Article

Coenzyme Q10 supplementation in infertile men with idiopathic asthenozoospermia: An open, uncontrolled pilot study

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Abstract

To clarify a potential therapeutic role of coenzyme Q(10) (CoQ(10)) in infertile men with idiopathic asthenozoospermia. Open, uncontrolled pilot study. Infertile men with idiopathic asthenozoospermia. CoQ(10) was administered orally; semen samples were collected at baseline and after 6 months of therapy. MAIN OUTCOME MEASURE (S): Semen kinetic parameters, including computer-assisted sperm data and CoQ(10) and phosphatidylcholine levels. CoQ(10) levels increased significantly in seminal plasma and in sperm cells after treatment. Phosphatidylcholine levels also increased. A significant increase was also found in sperm cell motility as confirmed by computer-assisted analysis. A positive dependence (using the Cramer's index of association) was evident among the relative variations, baseline and after treatment, of seminal plasma or intracellular CoQ(10) content and computer-determined kinetic parameters. The exogenous administration of CoQ(10) may play a positive role in the treatment of asthenozoospermia. This is probably the result of its role in mitochondrial bioenergetics and its antioxidant properties.

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... At the same time, CoQ10 levels increased about 3fold in seminal plasma (from 42.0 ± 5.1 to 127.1 ± 1.9 ng/mL, p < 0.05) and 2-fold in sperm cells (from 3.1 ± 0.4 to 6.5 ± 0.3 ng/10 6 cells, p < 0.005), supporting a cause-effect relationship between sperm motility and seminal CoQ10 concentrations. After a 6-months period of washout, seminal parameters reverted to levels comparable to those measured at baseline [14]. In a subsequent randomized, double-blind, placebo-controlled study, the same group studied the effect of daily administration of 200 mg of CoQ10 for 6 months in 28 subjects and 27 control subjects. ...
... The present review demonstrated a general positive effect of CoQ10 supplementation on seminal parameters. As regards CoQ10 monotherapy, sperm motility significantly increased in all the studies evaluated [9,[13][14][15][16][18][19][20][21][22][23] except one [17]. A significant increase in sperm concentration was also reported by some authors [13,16,[18][19][20]23], whereas the effects on normal morphology were lower [9,13,18,19,23]. ...
... As noted above, spermatozoa are susceptible to OS that is generated when seminal fluid scavenging mechanisms are overwhelmed by ROS [4]. CoQ10 supplementation significantly increases seminal coQ10 levels [14,15] and improves the antioxidant capacity of seminal fluid [13,17,18,20,21,23], improving both enzymatic and non-enzymatic germ cell protection systems. This appears critical in protecting sperm DNA from ROS damage, as demonstrated by some authors [11,25,28,29], who reported a significant reduction in the DFI after antioxidant treatment. ...
Article
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Infertility affects 15% of couples worldwide. A male factor is involved in 50% of cases. The etiology of male infertility is poorly understood, but there is evidence for a strong association between oxidative stress (OS) and poor seminal fluid quality. For this reason, therapy with antioxidants is one of the cornerstones of empirical treatment of male infertility. Coenzyme Q10 (CoQ10)—an essential cofactor for energy production with major antioxidant properties—is commonly used to support spermatogenesis in idiopathic male infertility. This systematic review aims to elucidate the usefulness of CoQ10 supplementation in the treatment of male infertility, particularly with regard to semen quality assessed by conventional and advanced methods, and pregnancy rates. All studies report a beneficial effect of CoQ10 supplementation on semen parameters, although randomized controlled trials are a minority. Moreover, the optimal dosage of CoQ10 or how it can be combined with other antioxidant molecules to maximize its effect is unknown. However, CoQ10 is still one of the most promising molecules to treat idiopathic male infertility and warrants further investigation.
... Раннее применение анализа ОССР в андрологии позволило обнаружить снижение антиоксидантной эффективности семенной плазмы у мужчин с бесплодием и статистически значимую корреляцию между связывающей способностью к гидроксильным радикалам и подвижностью сперматозоидов [18]. Кроме того, показано, что лечение пациентов с астенозо оспермией антиоксидантами приводит к улучшению качества эякулята [19,20] и частоты наступления беременности [20]. ...
... Раннее применение анализа ОССР в андрологии позволило обнаружить снижение антиоксидантной эффективности семенной плазмы у мужчин с бесплодием и статистически значимую корреляцию между связывающей способностью к гидроксильным радикалам и подвижностью сперматозоидов [18]. Кроме того, показано, что лечение пациентов с астенозо оспермией антиоксидантами приводит к улучшению качества эякулята [19,20] и частоты наступления беременности [20]. ...
... На основании ранее полученных результатов в нашей группе и данных других исследователей [20][21][22][23][24][25] основным критерием эффективности было выбрано улучшение подвижности сперматозоидов (общей и прогрессивной). ...
Article
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Objective: To evaluate the effectiveness of L-carnitine (LC) or L-acetyl-carnitine (LAC) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen. Design: Placebo-controlled, double-blind, randomized trial.Setting: Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Patient(s): Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 × 10 6 / mL, sperm forward motility < 50 %, and normal sperm morphology > 30 %; 59 patients completed the study.Intervention(s): Patients underwent a double-blind therapy of LC 3 g / d, LAC 3 g / d, a combination of LC 2 g / d + LAC 1 g / d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.Main Outcome Measure(s): Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.Result(s): Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.Conclusion(s): The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population (Fertil Steril ® 2005;84:662–71.©2005 by American Society for Reproductive Medicine.).
... In vivo studies performed on infertile men showed that dietary CoQ10 supplementation (150e400 mg CoQ10/ man daily) increased the CoQ10 levels in their seminal plasma and sperm cells. This in turn, improved the sperm concentration and motility in humans [21,37,38]. Moreover, in vitro studies performed in bovine [39], human [40] and rooster [41] subjects showed that the supplementation of semen extender with CoQ10 improved their sperm quality. ...
... Kelso et al. (1996) showed that the changes in the lipid composition of sperm in aging fowl were correlated with a reduction in the activities antioxidant enzymes [1]. Balercia et al. (2004) showed that CoQ10 supplementation (400 mg CoQ10/man) in infertile men increased sperm membrane phosphatidylcholine concentration and enhanced sperm quality [37]. Similar to the current, a study performed on infertile men showed that supplemental dietary CoQ10 (200 mg CoQ10/man) improved antioxidant enzyme activity and decreased oxidative stress in seminal plasma [20]. ...
... Kelso et al. (1996) showed that the changes in the lipid composition of sperm in aging fowl were correlated with a reduction in the activities antioxidant enzymes [1]. Balercia et al. (2004) showed that CoQ10 supplementation (400 mg CoQ10/man) in infertile men increased sperm membrane phosphatidylcholine concentration and enhanced sperm quality [37]. Similar to the current, a study performed on infertile men showed that supplemental dietary CoQ10 (200 mg CoQ10/man) improved antioxidant enzyme activity and decreased oxidative stress in seminal plasma [20]. ...
Article
In numerous studies it has been suggested that targeting mitochondria with specific compounds could efficiently inhibit various conditions associated with oxidative stress. The treatment of aged roosters with compounds such as coenzyme Q10 (CoQ10), may improve their reproductive performance by providing protection from oxidative stress. Therefore, this study was performed to assess the effect of supplemental dietary CoQ10 on the testicular function and fertility of aged broiler breeder roosters. A total of 36 roosters (47 weeks of age) were randomly divided into dietary treatments containing either 0, 300 or 600 mg CoQ10/kg diet. Three birds were allocated to each of four replicate groups in each dietary treatment. Between 47 to 54 weeks of age, ejaculates were obtained weekly from the three roosters in each replicate group. Samples in a replicate were pooled and analyzed as a single sample. Between 51 and 54 weeks of age, seminal plasma total antioxidant capacity (TAC), alanine amino transferase (ALAT) and aspartate amino transferase (ASAT) levels were assessed. Fertility, hatchability, and sperm penetration (SP) rates were likewise evaluated. Seminal volume, sperm concentration, sperm plasma membrane functionality, sperm plasma membrane integrity, seminiferous tubule diameter and seminiferous epithelium thickness exhibited quadratic increases in response to increasing levels of dietary CoQ10. Respectively, the 429.19, 433.33, 464.50, 613.50, 392.78 and 447.99 mg/kg dietary concentrations of CoQ10 provided the best results for each of the aforementioned variables. Also, other seminal traits, as well as testosterone concentration, fertility, and SP rates, displayed linear increases in response to the increasing levels of CoQ10. Dietary supplementation of CoQ10 linearly decreased seminal plasma ALAT and ASAT and linearly increased seminal plasma TAC. In conclusion, CoQ10 supplementation in the diet (a minimum of 300 mg CoQ10/kg diet) has the potential to improve the reproductive performance of aged broiler breeder roosters.
... Coenzyme Q10 (CoQ10) is concentrated in the mitochondria located in the midpiece of sperm, and the levels of this compound show a significant correlation with sperm count and motility. Furthermore, CoQ10 may be deficient in varicocele leading to higher sensitivity to oxidative damage (Balercia et al., 2004). Fructose, citric acid, vitamin C, vitamin B12 and zinc are related to increased damage to the sperm genetic material, synthesis of coenzymes, metabolism and energy production (Chia, Ong, Chua, Ho, & Tay, 2000;Dawson, Harris, Teter, & Powell, 1992;Moslemi & Tavanbakhsh, 2011). ...
... Administration of coenzyme Q10 to men with idiopathic asthenozoospermia results in an increase in sperm motility (Balercia et al., 2004). ...
... Nevertheless, the distribution of CoQ10 between intracellular and extracellular compartments appears to be an active process. Besides, there is a positive correlation between the level of coenzyme Q10 in seminal plasma and sperm motility (13). Consequently, it can be argued that in some cases, an increase in stress due to oxidation in spermatozoa can somehow suppress levels of CoQ10, which can negatively affect the bioenergetic effects on spermatogenesis. ...
... However, a deeper understanding of the molecular mechanism of coenzyme Q10 may lead to a greater understanding of infertility (13). In contrast, Littaru and colleagues (42) observed that the addition of coenzyme Q10 increased the level of ubiquinol-10 in circulating lipoproteins, while low-density lipoproteins in humans also increased resistance to lipid peroxidation, thereby reducing oxidative stress. ...
Article
Artificial insemination (AI) with frozen or cooled-stored semen plays a key role in the widespread distribution of germplasm of elite livestock resources and the protection of endangered species. Cryopreservation provides long-term preservation of sperm and also encourages a greater exchange of genetic material between distant populations. However, freezing has some detrimental effects on sperm, including premature induction of acrosome response, reduced sperm motility, reduced viability, and impaired sperm DNA integrity and fertility. The transition of the membrane phase occurs when the sperm cools down, and lipid accumulation damages the micro-domain, thereby impairing membrane functions, leaving a gap between the gel and the liquid membrane region. Coenzyme Q10 (CoQ10) is a vital lipophilic molecule found in all respiratory eukaryotic cells, including spermatozoa. When such a lipophilic antioxidant is added to the sperm, it can directly diffuse into the polyunsaturated lipid chain present in the plasma membrane, thereby affecting the structure and function of the sperm by generating energy and preventing reactive oxygen. Coenzyme Q10 treatment of sperm from various species improves sperm quality during cryopreservation and cooled-stored condition. It is, however, unclear how this antioxidant affects sperm to improve survival during freezing or cooled-stored condition. Thus, this review highlights the potential protective mechanisms of coenzyme Q10 action during the sperm freezing process.
... ROS are highly reactive molecules produced during normal cellular metabolism and physiology, formed due to the incomplete reduction of oxygen [5]. In seminal plasma, ROS play a fundamental physi-ologic role in several sperm functions, such as the development, maturation, and capacitation of spermatozoa, as well as the acrosome reaction and fertilization [6]. Sperm cells and leukocytes are the main sources of ROS in seminal plasma. ...
... Similar findings were reported by Safarinejad and colleagues [16,26] after administration of CoQ10 (200 mg) for 26 weeks in men with OAT and 300 mg daily for 26 weeks in men with OAT. Balercia et al. [1,6] reported an increase in CoQ10 levels in seminal plasma and improvements in sperm parameters following administration of CoQ10 (200 mg/day) for 6 months. In contrast, in an open-label prospective study, men with OAT who were treated with CoQ10 (600 mg) for 12 months showed significant improvements in sperm progressive motility, concentration, and morphology at the 12-month follow-up [27]. ...
Article
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Objective: Oxidative stress contributes to male infertility, and antioxidants have been recommended for treating idiopathic oligoasthenoteratospermia (OAT). There is, however, a lack of agreement on the type, dosing, and use of individual antioxidants or combinations thereof. The purpose of this study was to compare the effects of two doses of coenzyme Q10 (CoQ10) on semen parameters and antioxidant status in men with idiopathic OAT. Methods: In this prospective study, patients with idiopathic OAT received 200 mg/day (n = 35) or 400 mg/day (n = 30) of CoQ10 orally for 3 months. All patients underwent semen analysis according to the fifth editions of the World Health Organization criteria. Total antioxidant capacity (TAC), catalase (CAT) activity, and superoxide dismutase (SOD) activity were measured both before and after treatment. Results: Treatment with CoQ10 (200 mg/day or 400 mg/day) resulted in a significant increase in sperm concentration from baseline (8.22 ± 6.88 to 12.53 ± 8.11 million/mL, p= 0.019; 7.58 ± 5.41 to 12.33 ± 6.1 million/mL, p= 0.002, respectively), progressive motility (16.54% ±9.26% to 22.58% ±10.15%, p=0.011; 14.22% ±12.85% to 26.1% ±14.52%, p= 0.001, respectively), and total motility (25.68% ± 6.41% to 29.96% ± 8.09%, p= 0.016; 23.46% ± 12.59% to 34.82% ± 14.17%, p= 0.001, respectively). CoQ10 therapy also increased TAC (p= 0.009, p= 0.001, respectively), SOD activity (p= 0.004, p= 0.001, respectively), and CAT activity (p= 0.039, p= 0.024, respectively). Furthermore, antioxidant measures correlated significantly with seminal fluid parameters (r = 0.36-0.76). Conclusion: CoQ10 supplementation improved semen parameters and antioxidant status in men with idiopathic OAT, with a greater improvement shown in men who took 400 mg/day than in those who took 200 mg/day.
... Coenzyme Q10 is concentrated in the mitochondria of the midpiece of sperm, and its levels show a significant correlation with sperm count and with sperm motility. Furthermore, the CoQ10 may be deficient in varicocele leading to higher sensitivity to oxidative damage (Balercia et al., 2004). Fructose, citric acid, vitamin C, vitamin B12 and zinc are related to increased damage to the sperm genetic material, synthesis of coenzymes, metabolism and energy production (Chia, Ong, Chua, Ho, & Tay, 2000;Dawson, Harris, Teter, & Powell, 1992;Moslemi & Tavanbakhsh, 2011). ...
... Administration of coenzyme Q10 to men with idiopathic asthenozoospermia results in an increase in sperm motility (Balercia et al., 2004). ...
Article
OBJECTIVE: Varicocele has adverse effects on spermatogenesis and to date is considered as the first cause of male infertility. Many factors nega- tively affecting semen quality act through decreasing energy availability by mitochondrial dysfunction and sperm are also vulnerable to reactive oxy- gen species because their accumulation leads to membrane damage, insta- bility and functional alterations causing cell death. DESIGN: To evaluate, utilizing a randomized double-blind placebo controlled trial, the effect of supplementation with selected naturally com- pounds on pregnancy rate and sperm quality. The effect was evaluated in sub- jects with oligo or asthenoteratozoospermia, as well as with or without varicocele. MATERIALS AND METHODS: With a block randomization 104 patients were enrolled: 52 had grade I-III varicocele and 52 were not affected. Patients belonging to these 2 groups were further divided in two groups consisting of the supplementation arm and the placebo arm. The supplementation formu- lation consisted of 1g of L-carnitine, 725mg of fumarate, 500mg of acetyl-L- carnitine, 1g of fructose, 50mg of citric acid, 50mcg of selenium, 20mg of coenzyme Q10, 90mg of vitamin C, 10mg of zinc, 200mcg of folic acid & 1.5mcg of vitamin B12. Spermogram evaluation was done at the beginning of treatment and at the end. RESULTS: Adverse events occurred only in the treatment group: 4 pa- tients had nausea and 3 vertigo or headache. Twelve pregnancies occurred during follow-up time: 10 in supplementation group (9 non- varicocele and 1 varicocele) and 2 in placebo group (1 non-varicocele and 1 varicocele). One spontaneous abortion was reported in placebo arm. Mean changes of number of sperm (106 x mL) after treatment were 1.7 in the placebo group and 9.8 in the supplemented group (p1⁄40.0186). Mean changes of sperm concentration (106 x mL) after treatment were 13.0 in the placebo group and 46.9 in the supplemented group (p1⁄40.0117). Mean changes of progressive motility of sperm (%) were 1.7 in the placebo group and 5.9 in the supplement group (p1⁄40.0088). Mean changes of total motility of sperm (%) were 1.6 in the placebo group and 7.3 in the supplement group (p1⁄40.0120). Analyzing typical and atypical morphology there was, respectively, a difference of -6.1 and 5.9 in the placebo group while -6.7 and 3.6 in the supplement group. CONCLUSIONS: Oxidative stress is a cause of male infertility with significant negative effect on semen parameters and varicocele is an additional cause of poor sperm quality. The use of carnitines and other functional substances is an efficacious strategy to handle male infer- tility. All sperm parameters significantly increased in treated subjects, while a strong increase in pregnancy rate wa
... Coenzyme Q10 (CoQ10) is concentrated in the mitochondria located in the midpiece of sperm, and the levels of this compound show a significant correlation with sperm count and motility. Furthermore, CoQ10 may be deficient in varicocele leading to higher sensitivity to oxidative damage (Balercia et al., 2004). Fructose, citric acid, vitamin C, vitamin B12 and zinc are related to increased damage to the sperm genetic material, synthesis of coenzymes, metabolism and energy production (Chia, Ong, Chua, Ho, & Tay, 2000;Dawson, Harris, Teter, & Powell, 1992;Moslemi & Tavanbakhsh, 2011). ...
... Administration of coenzyme Q10 to men with idiopathic asthenozoospermia results in an increase in sperm motility (Balercia et al., 2004). ...
Article
Full-text available
Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow-up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.
... Therefore, CoQ10 could be a useful parameter for its energetic, antioxidant and anti-inflammatory properties. Despite the last aspect justified trials exploring CoQ10 effects on inflammatory markers, in metabolic and cardiovascular diseases [40], the other two roles represented the rationale for some interventional trials, in the field of infertility, which demonstrated a beneficial effect of CoQ10 administration on sperm motility [41,42]. ...
... A. Controls (normozoospermic) 12 patients, median age and interquartile range 34 (33)(34)(35)(36)(37)(38)(39)(40)(41) years, BMI 21 (18)(19)(20)(21)(22)(23) kg/m 2 , 33% smokers. B. Varicocele (VAR), 29 patients, median age and interquartile range 33 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) years, kg/m 2 , 40% smokers. ...
Article
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Oxidative and inflammatory damage underlie several conditions related to male infertility, including varicocele. Free light chains of immunoglobulins (FLCs) are considered markers of low-grade inflammation in numerous diseases. Coenzyme Q10 (CoQ10), a lipidic antioxidant and anti-inflammatory compound, is involved in spermatozoa energy metabolism and motility. We aimed to evaluate FLCs’ seminal levels in patients with varicocele in comparison to control subjects and to correlate them with CoQ10 and Total Antioxidant Capacity (TAC) in human semen. Sixty-five patients were enrolled. Semen analysis was performed; patients were divided into three groups: controls, 12 normozoospermic patients, aged 34 (33–41) years; varicocele (VAR), 29 patients, aged 33 (26–37) years; and idiopathic, 24 oligo-, astheno- and oligoasthenozoospermic patients aged 37 (33.5–40.5) years. FLCs (κ and λ) were assayed by turbidimetric method; CoQ10 by HPLC; TAC by spectrophotometric method. λ FLCs showed a trend toward higher levels in VAR vs. controls and the idiopathic group. VAR showed a trend toward lower κ FLCs levels vs. the other two groups. When comparing κ/λ ratio, VAR showed significantly lower levels vs. controls and idiopathic. Moreover, CoQ10 seminal levels showed higher levels in VAR and idiopathic compared to controls. Data reported here confirm lower levels of κ/λ ratio in VAR and suggest a possible application in personalized medicine as clinical biomarkers for male infertility.
... CoQ10 is found naturally in the seminal fluid and plays a central role in enhancing several key features of semen. Deficiency in CoQ10 has been linked to impaired sperm parameters [13]. Therefore, it has been used in several studies as a treatment for infertile men. ...
... This in turn can counteract oxidative damage and sustain the function of Leydig cells protecting testosterone secretion [46]. The key application of CoQ10 in the testis is to increase the levels of CoQ10 and its reduced form, ubiquinol, in the semen [13]. Ubiquinol is a potent fat-soluble antioxidant that can regenerate other antioxidants including vitamins E and C [47]. ...
Article
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Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n=7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v:v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.
... This in turn can counteract oxidative damage and sustain the function of Leydig cells protecting testosterone secretion [34] . The key application of CoQ10 in the testis is to increase the levels of CoQ10 and its reduced form, ubiquinol, in the semen [35].Ubiquinol is a potent fat-soluble antioxidant that can regenerate other antioxidants including vitamins E and C [36]. It also eliminates peroxyl radicals resulting from the lipid peroxidation process [37].It also reduces the levels of follicle-stimulating hormone and luteinizing hormone [38,39], The investigators' highlight that a lower serum follicle-stimulation hormone implies better spermatogenesis [40]. ...
... orBecause of dramatically reduced serum hormone levels (LH, FSH, and testosterone levels), testis weight by direct desensitization of the HPG axis [19].perhaps significant decreases in germ cells, daily sperm production, total support capacity of Sertoli cells, Sertoli efficiency and meiotic index, and an increase in the coefficient of mitosis indicated germ cell loss, which may have occurred through apoptotic mechanisms [20].coadministration of kisspeptin and ubiquinone resulted in a significant enhancement in the total sperm count,elongated spermatid and daily sperm production, the improvements may be due CoQ10 act as an antioxidant, an energy booster, a membrane stabilizer, and a regulator of mitochondrial permeability transition pores [36].The majority of CoQ10 in sperm cells is concentrated in the mitochondria of the mid piece, and energy-dependent activities in the sperm cell are dependent on CoQ10 availability [45].CoQ10 levels in seminal fluid have a direct relationship with sperm parameters [46].Due to its participation in mitochondrial bioenergetics and antioxidant characteristics, exogenous treatment of CoQ 10 raises both ubiquinone and ubiquinol levels in the sperm and can be useful in enhancing sperm kinetic aspects in patients with idiopathic asthenozoospermia [14,35]. The findings show that supplementing with Ubiquinol aids in boosting sperm count and motility [47].Reduced oxidative damage in the presence of the lipophilic antioxidant ubiquinol may explain why testicular cells release a normal quantity of testosterone. ...
Article
Objectives:. to investigates the effects of pulsatile Kisspeptin administration for12 days on gonadotropin and testosterone production and maturation of immature rat male gonads, as well as to assess the protective role of ubiquinone 10 when rats were exposed to Kisspeptin in the male reproductive system during the prepubertal phase. Materials & methods: thirty-six male rats were used in the experiment. The rats divided into four groups (eight each) ,the first group were given DMSO as control, the second group were given kisspeptin as experimental,the third group were given kisspeptin + ubiquinone as treatment and the fourth group was given ubiquinone only as care.At the end of the experiment, all rats in each group were sacrificed. after this, Plasma LH, FSH and testosterone concentrations were measured, while total spermatid head count,elongated spermatid and daily sperm production were calculated. Results. At the end of the treatments, the result shows a significant decrease in follicular stimulating hormone(FSH), Luteinizing hormone (LH)and testosterone hormone while show significant increase in Inhibin B in male rats treated with 50nmol/kg B.W of kisspeptin during the pre pubertal stage compared with other groups. coadministration of ubiquinone with kisspeptin results in an improvement in LH, FSH ,testosterone and Inhibin B levels in the present study.while other results concerning a total number of spermatid heads, elongated spermatid and daily sperm production show a significant decrease in male rats treated with 50nmol/kg B.W of kisspeptin compare with other groups. coadministration of ubiquinone with kisspeptin results in a significant elevation in all parameters treated studied.
... These patients also simultaneously attended movement disorder school. The subjects were administered oral dosages of CoQ10 in concentrations 300 mg/day, 600 mg/day, and 1200 mg/day for 16 months until they reached a point where a rescue treatment became vital [61]. The UPDRS (Unified Parkinson Disease Rating Scale) was employed to measure the difference in total scores between the end of the study and the baseline as reported in the literature [53]. ...
... Since CoQ10 is a compound known to have high lipophilicity, high molecular weight, and heat-sensitive in nature, yoghurt is considered the best medium for the fortification of CoQ10 [48]. The consumption of CoQ10 by people affected with idiopathic as then azoospermia leads significant increase in the ubiquinone and ubiquinol levels in semen with an inverse relationship between the ratio of Ubiquinone to ubiquinol [61]. With the supplementation of CoQ10 for two weeks to healthy volunteers, the total antioxidant capacity and the plasma CoQ10 concentrations in the human body were observed to be elevated [69]. ...
Article
Full-text available
Coenzyme Q10 (CoQ10) is an antioxidant, fat-soluble component present in the mitochondrial cells. It provides beneficial results in the treatment of male infertility. In the current scenario, the sedative lifestyle, diet and stress in human lead to excessive free radicals (ROS), leading to health aliments. The review is conducted to compare the effect of different fortification methods of CoQ10 in the Yogurt. The study showed that nanoparticles form of CoQ10 in yogurt showed higher bioaccesiblity rates in humans, and the microencapsulation of CoQ10 showed a low amount of Ubiquinone released during its shelf life. The functional Yogurt produced by the Monascus-fermented soybean powder (MFSP) co-fermentation has been shown to have high free radicals scavenging activity. Thus, the review observes that each fortified sample is useful in its way as CoQ10 supplements. Further studies must be done for accurate conclusions on its effect on male infertility, and other fortification media can be explored.
... These patients also simultaneously attended movement disorder school. The subjects were administered oral dosages of CoQ10 in concentrations 300 mg/day, 600 mg/day, and 1200 mg/day for 16 months until they reached a point where a rescue treatment became vital [61]. The UPDRS (Unified Parkinson Disease Rating Scale) was employed to measure the difference in total scores between the end of the study and the baseline as reported in the literature [53]. ...
... Since CoQ10 is a compound known to have high lipophilicity, high molecular weight, and heat-sensitive in nature, yoghurt is considered the best medium for the fortification of CoQ10 [48]. The consumption of CoQ10 by people affected with idiopathic as then azoospermia leads significant increase in the ubiquinone and ubiquinol levels in semen with an inverse relationship between the ratio of Ubiquinone to ubiquinol [61]. With the supplementation of CoQ10 for two weeks to healthy volunteers, the total antioxidant capacity and the plasma CoQ10 concentrations in the human body were observed to be elevated [69]. ...
Article
1. Abstract Coenzyme Q10 (CoQ10) is an antioxidant, fat-soluble component present in the mitochondrial cells. It provides beneficial results in the treatment of male infertility. In the current scenario, the sedative lifestyle, diet and stress in human lead to excessive free radicals (ROS), leading to health aliments. The review is conducted to compare the effect of different fortification methods of CoQ10 in the Yogurt. The study showed that nanoparticles form of CoQ10 in yogurt showed higher bioaccesiblity rates in humans , and the microencapsulation of CoQ10 showed a low amount of Ubiquinone released during its shelf life. The functional Yogurt produced by the Monascus-fermented soybean powder (MFSP) co-fermentation has been shown to have high free radicals scavenging activity. Thus, the review observes that each fortified sample is useful in its way as CoQ10 supplements. Further studies must be done for accurate conclusions on its effect on male infertility, and other fortification media can be explored.
... Antioxidants have been successfully used to treat male infertility and to improve motility and membrane integrity in cryopreservation process in man, bull, ram, goat, boar and dog (Bansal & Bilaspuri 2010). Among substances with recognised antioxidants effect, coenzyme Q (CoQ) has been identified as a natural lipophilic organic compound preventing OS on spermatozoa; it is present in the mitochondria of spermatozoa and in seminal plasma and its addition to semen has given good results in preventing male infertility (Balercia et al. 2004). The CoQ occurs in three redox states: ubichinone, ubisemichinone and ubichinol, which allow it to act both as antioxidant and as pro oxidant. ...
... A recent study shows that serum concentration of CoQ 10 in horse increases with oral supplementation (Sinatra et al. 2013). This way of administration seems to give statistically significant improvements in human species for motility parameters in semen and a positive correlation was found between treatment duration with CoQ 10 and sperm count, motility and morphology (Balercia et al. 2004); these improvements seem to be due by a more active spermatogenesis by the seminiferous tubules and to an alteration of the reproductive hormone profiles (Safarinejad 2009). Indeed, testes have a very low level of oxygen tension and this is further reduced by the activity of mitochondria and germ cells involved in the spermatogenesis (Aitken & Roman 2008). ...
Article
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Several studies reveal that coenzyme Q (CoQ) and vitamin E (Vit. E) act against oxidative deterioration, and that CoQ restores the active and antioxidant form of Vit. E. These two antioxidants, acting against lipid peroxidation, seem to be able to improve motility parameters of spermatozoa. The objective of this study is to evaluate the addition of CoQ and Vit. E to semen extender for equine spermatozoa in order to evaluate possible effects on semen motility. First, immediately after collection, semen samples were diluted with 1mM of CoQ and 1mM of CoQ plus 1mM of Vit. E and prepared for frozen storage in liquid nitrogen. After thawing (37 °C/30 s), samples were maintained at 37 °C and subjected to analysis after 0, 2 and 4 h for motility parameters with CASA (Computer-Assisted Sperm Analysis) method. In a second experiment, after the collection, semen samples were diluted with 1mM of CoQ, in presence or absence of seminal plasma where Vit. E is normally present, and prepared for cooled storage at 4 °C. The effects on motility parameters were determined with CASA at 0, 24, 31 and 48 h after collection. During the analysis, samples were kept at 4 °C. The CASA variables were examined with a mixed linear model. No improvement (p > .05) in motility parameters results from the addition of CoQ and Vit. E in frozen or cooled-stored equine semen when compared to control group.
... In vitro and in vivo studies done by Lewin and Lavon (1997) reported a significant increase in sperm cell motility after treatment with coenzyme Q10 in humans (Lewin and Lavon 1997). Additionally, some other recent studies also have shown that CoQ10 can increase sperm health, particularly sperm motility (Balercia et al. 2004;Balercia et al. 2009;Safarinejad 2009;Mancini and Balercia 2011). ...
Chapter
In a number of lower organisms and seasonal breeders, availability of food is a key determinant in shaping the time for reproduction and fertility. Therefore, food and nutrition strongly affect fertility, even in nonseasonal breeders. Eating a balanced diet is the key to good overall health. Food habits and their inherent components vary greatly across the globe. Making nutritious food a part of the regular diet can ameliorate health and upkeep fertility. Deficiency of nutrients and antioxidants can decrease fertility as various reports have supported the role of antioxidants in fertility. This chapter provides a comprehensive coverage of dietary elements that provide essential nutrients, cofactors, and antioxidants for the maintenance of good reproductive potential and fertility and improve prophylaxis against infertility.
... Exogenous administration of UQ 10 can increase sperm cell motility and the mean pregnancy rate. Its positive role in the treatment of male infertility also relies on the antioxidant properties and bioenergetics (Balercia et al., 2004;Mancini et al., 2005;Balercia et al., 2009;Mancini and Balercia, 2011;Safarinejad, 2012). As a good immunomdulator, UQ 10 has been used to treat chronic gingivitis and periodontitis (Chatterjee et al., 2012;Hans et al., 2012). ...
Article
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Plastoquinone (PQ) and ubiquinone (UQ) are two important prenylquinones, functioning as electron transporters in the electron transport chain of oxygenic photosynthesis and the aerobic respiratory chain, respectively, and play indispensable roles in plant growth and development through participating in the biosynthesis and metabolism of important chemical compounds, acting as antioxidants, being involved in plant response to stress, and regulating gene expression and cell signal transduction. UQ, particularly UQ10, has also been widely used in people’s life. It is effective in treating cardiovascular diseases, chronic gingivitis and periodontitis, and shows favorable impact on cancer treatment and human reproductive health. PQ and UQ are made up of an active benzoquinone ring attached to a polyisoprenoid side chain. Biosynthesis of PQ and UQ is very complicated with more than thirty five enzymes involved. Their synthetic pathways can be generally divided into two stages. The first stage leads to the biosynthesis of precursors of benzene quinone ring and prenyl side chain. The benzene quinone ring for UQ is synthesized from tyrosine or phenylalanine, whereas the ring for PQ is derived from tyrosine. The prenyl side chains of PQ and UQ are derived from glyceraldehyde 3-phosphate and pyruvate through the 2-C-methyl-D-erythritol 4-phosphate pathway and/or acetyl-CoA and acetoacetyl-CoA through the mevalonate pathway. The second stage includes the condensation of ring and side chain and subsequent modification. Homogentisate solanesyltransferase, 4-hydroxybenzoate polyprenyl diphosphate transferase and a series of benzene quinone ring modification enzymes are involved in this stage. PQ exists in plants, while UQ widely presents in plants, animals and microbes. Many enzymes and their encoding genes involved in PQ and UQ biosynthesis have been intensively studied recently. Metabolic engineering of UQ10 in plants, such as rice and tobacco, has also been tested. In this review, we summarize and discuss recent research progresses in the biosynthetic pathways of PQ and UQ and enzymes and their encoding genes involved in side chain elongation and in the second stage of PQ and UQ biosynthesis. Physiological functions of PQ and UQ played in plants as well as the practical application and metabolic engineering of PQ and UQ are also included.
... CoQ10 can be present in the reduced form, ubiquinol, which acts as a potent antioxidant, and in the oxidized form, ubiquinone (Lanzafame et al. 2009). Oral supplementation of CoQ10 for 6 months in infertile men with idiopathic asthenozoospermia increased levels of CoQ10 in seminal plasma and sperm cells and also increased sperm motility (Balercia et al. 2004). CoQ10 concentrations in the seminal plasma are directly correlated with sperm count and motility (Lanzafame et al. 2009). ...
Chapter
Physiological levels of reactive oxygen species (ROS) are required for proper functioning of the male and female reproductive system. However, imbalances between ROS production and antioxidant systems induce oxidative stress, which can jeopardize the quality of the gamete and the developing embryo and cause many pregnancy disorders, such as spontaneous abortion, recurrent pregnancy loss, preeclampsia, fetal embryopathies, and intrauterine growth restriction. This review discusses the adverse effect of ROS-induced oxidative stress in assisted reproductive technologies (ART) outcome, ROS generated in vitro by gametes and embryos, and ROS generated by external sources in the in vitro fertilization (IVF) laboratory and the protocols used, including gamete/embryo handling, composition and pH of culture media, temperature and oxygen concentration during incubation, centrifugation and freeze-thaw protocols, as well as visible light. Studies on oral supplementation of enzymatic and nonenzymatic antioxidants are discussed. Although there is no one antioxidant that is considered the best choice for improving ART outcomes, some antioxidants show promising results. Additional well-designed trials are needed to determine the appropriate type(s) and concentration of antioxidant(s) that would be helpful to infertile patients with various etiologies. Studies are also warranted in the improvement of ART protocols to minimize ROS formation during assisted reproduction.
... CoQ10 acts as an antioxidant by inhibiting lipid peroxidation and DNA oxidation, thus is capable of strengthening endogenous antioxidant system within a cell [15]. CoQ10 supplementation has been shown to improve cardiovascular function and male fertility [16][17][18]. Reduced concentrations of CoQ10 in plasma have been associated with hypogonadism and altered levels of other steroid hormones [19]. Decrease in CoQ10 level is commonly observed in individuals in late 30th and appears to co-occur with the age-related decline in fertility and increased rate of embryo aneuploidy, suggesting a contribution of the reduced expression of CoQ10 to ovarian ageing [20]. ...
Article
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Background: Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. Methods: This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age < 35, poor ovarian reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. Results: A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p < 0.05. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical pregnancy and live birth rates per embryo transfer and per one complete stimulation cycle tended to be higher in CoQ10 group but did not achieve statistical significance. Conclusion: Pretreatment with CoQ10 improves ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.
... Previous studies have assessed the use of l-carnitine alone as well as various combination therapies as an effective way of improving semen analysis results [34][35][36][37][38][39][40][41][42]. However, a direct contrast with a combination of various micronutrients and, consequently, a quantification of the effects, has not yet been assessed in the framework of a research study. ...
Article
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Background There are reports showing that l-carnitine alone or in combination with other micronutrients improve sperm parameters. However, comparative studies are still lacking. This study was carried out to compare the short term effects of a combination of eight micronutrients including l-carnitine vs. a mono-substance (l-carnitine alone) on sperm parameters. Methods This was a prospective, open-labelled, nonrandomized study that included male subjects (20 to 60 years) with at least 1 year of subfertility and at least one pathological semen analysis who received 3 months treatment with a mono-substance (500 mg l-carnitine/twice a day, n = 156) or a combined compound (440 mg l-carnitine + 250 mg l-arginine + 40 mg zinc + 120 mg vitamin E + 80 mg glutathione + 60 μg selenium + 15 mg coenzyme Q10 + 800 μg folic acid/once a day, n = 143) for the same time period. Sperm parameters were analyzed before and after treatment and groups comparisons performed. ResultsBaseline characteristics were similar among studied groups (age and body mass indices). Semen parameters (volume, density, overall progressive motility [including slow and fast motility]) and percentage of sperm with normal morphology improved after 3 months in both groups as compared to baseline. However, relative change (expressed as % increase of absolute values) for sperm density and overall progressive motility (including fast motility) was found to be higher for the combined micronutrient treatment group as compared to the mono-treatment using l-carnitine alone. Conclusion Both analyzed groups displayed a positive short term effect on all sperm parameters; however effect on density and motility was significantly better for the combined formulation. There is need for more research in this matter that includes long term outcome data. Trial registrationRetrospectively registered at ISRCTN (7th October 2016). Study ID: ISRCTN48594239
... A number of nutritional therapies have been evaluated the efficacy of antioxidants such as carnitine, arginine, zinc, selenium, vitamin B-12, vitamin C, vitamin E, glutathione and coenzyme Q10 in male infertility (Agarwal et al., 2004;Balercia et al., 2004;Crha et al., 2003). ...
Article
Sertraline is an antidepressant medication used extensively in the therapy of depression. The present investigation was intended to estimate the actual protective role of wheat germ oil on sertraline‐caused testicular injury in albino rats. Sertraline (human therapeutic dose, 15.63 mg/kg) was orally administrated to rats for 28 successive days. Sertraline‐administered rats were concurrently supplemented with wheat germ oil (human therapeutic dose, 68.75 mg/kg) for 28 successive days. Sertraline administration induced an elevation in testicular DNA damage and acute testicular damage illustrated by the histopathological alterations including marked degeneration and necrosis of germ cells lining seminiferous tubules, as well as interstitial oedema, congestion of interstitial blood vessel. Wheat germ oil administration potentially mitigated the histopathological alterations of sertraline‐administered rats. Lipid peroxidation, oxidative stress biomarker, showed a significant elevation in testicular tissue of sertraline‐administered rats. Furthermore, glutathione content and catalase activity were decreased in testicular tissue of sertraline‐administered rats. Serum testosterone level was elevated in sertraline‐administered rats. Wheat germ oil significantly reduced lipid peroxidation of testicular tissue and improved the antioxidant defences. Finally, wheat germ oil has a preventive role against testicular damage induced by sertraline in rats probably via its potential to prevent reactive oxygen species.
... Additionally, the antioxidant supplement should augment the scavenging capacity of seminal plasma and reduce levels of seminal ROS [Zini et al. 2009]. Oral treatment with antioxidants such as vitamins E, C, A, B complex, coenzyme Q10 (CoQ10), ubiquinol, glutathione, L-carnitine, lactoferrin, β-carotene, lycopene, pantothenic acid, α-lipoic acid, N-acetyl-cysteine, selenium, zinc, copper or supplements containing a combination of these antioxidants have been used with success to varying degrees [Hughes et al. 1998; Balercia et al. 2004; Greco et al. 2005; Piomboni et al. 2008; Ghanem et al. 2010; Wang et al. 2010; Zini et al. 2010; Moslemi and Tavanbakhsh, 2011; Chen et al. 2012; Safarinejad, 2012; WalczakJedrzejowska et al. 2013; Durairajanayagam et al. 2014; Haghighian et al. 2015; Thakur et al. 2015]. In a randomized, triple-blind, placebo-controlled clinical trial, Haghighian and colleagues observed that antioxidant therapy in the form of α-lipoic acid supplementation in infertile men improved semen parameters (sperm count, concentration and motility) and seminal levels of total antioxidant capacity (TAC) and MDA [Haghighian et al. 2015]. ...
Article
Full-text available
The diagnosis of male infertility relies largely on conventional semen analysis, and its interpretation has a profound influence on subsequent management of patients. Despite poor correlation between conventional semen parameters and male fertility potential, inclusion of advanced semen quality tests to routine male infertility workup algorithms has not been widely accepted. Oxidative stress is one of the major mediators in various etiologies of male infertility; it has deleterious effects on spermatozoa, including DNA damage. Alleviation of oxidative stress constitutes a potential treatment strategy for male infertility. Measurement of seminal oxidative stress is of crucial role in the identification and monitoring of patients who may benefit from treatments. Various tests including reactive oxygen species (ROS) assay, total antioxidant capacity (TAC) assay or malondialdehyde (MDA) assay used by different laboratories have their own drawbacks. Oxidation-reduction potential (ORP) is a measure of overall balance between oxidants and antioxidants, providing a comprehensive measure of oxidative stress. The MiOXSYS™ System is a novel technology based on a galvanostatic measure of electrons; it presents static ORP (sORP) measures with static referring to the passive or current state of activity between oxidants and antioxidants. Preliminary studies have correlated sORP to poor semen qualities. It is potentially useful in prognostication of assisted reproductive techniques outcomes, screening of antioxidants either in vivo or during IVF cycles, identification of infertile men who may benefit from treatment of oxidative stress, and monitoring of treatment success. The simplified laboratory test requiring a small amount of semen would facilitate clinical application and research in the field. In this paper, we discuss the measurement of ORP by the MiOXSYS System as a real-time assessment of seminal oxidative stress, and argue that it is a potential valuable clinical test that should be incorporated into the male infertility workup and become an important guide to the treatment of oxidative stress-induced male infertility.
... Numerous studies have documented that dietary antioxidants such as coenzyme Q, vitamin E, glutathione and vitamin C/food supplements (arginine, vitamin B12, selenium, zinc etc.) protect spermatozoa from oxidative stress, increase sperm quality, inhibit defective sperm formation and promote normal sperm production (Balercia et al., 2004;Crha et al., 2003;McPherson, Shehadeh, Fullston, Zander-Fox, & Lane, 2019). ...
Article
Full-text available
Bisphenol A (BPA) is a well‐known endocrine disruptor that imposees adverse effects on male fertility via interacting with germ cells of testis. Objectives of present study were to investigate the possible protective effects of hydroethanolic Murraya koenigii leaves extract (HEMKLE) against BPA‐induced testicular damage and apoptosis in mice. Male Balb/c mice were divided into four different groups: Group I (control), Group II (HEMKLE), Group III (BPA) and Group IV (HEMKLE + BPA). Group III (BPA) showed significant decrease in sperm parameters, germ cell number along with increased lipid peroxidation (LPO) and reactive oxygen species (ROS). A significant decrease in antioxidant enzymes activity was also observed in Group III (BPA) animals. mRNA expression study revealed significant decrease in the expression of Bcl‐2 and increase in expressions of caspase‐9 and caspase‐3, thus clearly demonstrate BPA‐induced apoptosis. In addition, HEMKLE co‐administration to BPA‐treated mice showed a significant increase in sperm parameters, germ cell number, decreased levels of LPO and ROS, increased antioxidant enzymes activity in Group IV (HEMKLE + BPA). Also, mRNA expression study showed a significant increase in Bcl‐2 and decrease in caspase‐9 and caspase‐3 gene expressions in Group IV (HEMKLE + BPA). Thus, the present study suggests that HEMKLE intervention provides protection against BPA‐induced oxidative stress and apoptosis.
... Balercia et al [16] evaluated the concentration of CoQ10 in the seminal fluid and found increased CoQ10 levels in the patients after supplementation. A study also concluded that CoQ10 levels in the blood as well as in the seminal fluid increases after three or six months of supplementation [24]. ...
Article
Full-text available
Purpose: Oxidative stress and sperm DNA fragmentation (SDF) are potential contributing factors for idiopathic male infertility. Coenzyme Q10 (CoQ10) have been reported to be effective in the treatment of idiopathic male infertility, in general, owing to its antioxidant properties. Thus, the present study intends to investigate the effects of CoQ10 therapy on semen parameters, oxidative stress markers and SDF in infertile men, specifically with idiopathic oligoasthenozoospermia (OA). Materials and methods: In this case-control study, sixty-five infertile patients with idiopathic OA and forty fertile men (control) were included. All participants underwent semen analysis based on the World Health Organization guidelines (5th edition, 2010). Patients received CoQ10 at the dose of 200 mg/d orally for three months. Seminal plasma CoQ10, total antioxidant capacity (TAC), total reactive oxygen species (ROS), glutathione peroxidase (GPx), and SDF levels were measured in controls (baseline) and infertile patients pre- and post-CoQ10 treatment. Results: CoQ10 treatment for three months significantly improved sperm concentration (p<0.05), progressive motility (p<0.05), total motility (p<0.01), seminal fluid CoQ10 concentration (p<0.001), TAC (p<0.001), and GPx (p<0.001) levels in infertile men with OA. Further, ROS level (p<0.05) and SDF percentage (p<0.001) were reduced in OA patients as compared to the baseline. CoQ10 levels also correlated positively with sperm concentration (r=0.48, p=0.01) and total motility (r=0.59, p=0.003) while a negative correlation was recorded between SDF and sperm motility (r=-0.54, p=0.006). Conclusions: CoQ10 supplementation for three months could improve semen parameters, oxidative stress markers and reduce SDF in infertile men with idiopathic OA.
... Reduced PC content can affect the antioxidant enzy me system in sperm and further lead to reduced sperm vitality, which may be a potential mechanism of asthenospermia (Balercia et al., 2004;Kelso, Redpath, Noble, & Speake, 1997). Therefore, we hypothesized that PC may reduce o xidative stress during sperm cryopreservation and thus improve sperm quality. ...
Article
Full-text available
Donkeys are indispensable livestock in China because they have transport function and medicinal value. With the popularization of artificial insemination on donkeys, semen cryopreservation technology has gradually become a research hotspot. Seminal plasma is a necessary medium for transporting sperm and provides energy and nutrition for sperm. Seminal plasma metabolites play an important role in the process of sperm freezing, and also have an important impact on sperm motility and fertilization rate after freezing and thawing. In this study, liquid chromatography‐tandem mass spectrometry (LC‐MS / MS) analysis was used to compare the metabolic characteristics of seminal plasma of high freezability (HF) and low freezability (LF) male donkeys. We identified 672 metabolites from donkey seminal plasma, of which 33 metabolites were significantly different between the two groups. Metabolites were identified and categorized according to their major chemical classes, including homogeneous non‐metal compounds, nucleosides, nucleotides, and analogues, organosulfur compounds, phenylpropanoids and polyketide, organoheterocyclic compounds, organic oxygen compounds, benzenoids, organic acids and derivatives, lipids and lipid‐like molecules, organooxygen compounds, alkaloids and derivatives, organic nitrogen compounds. The results showed that the contents of phosphatidylcholine, piceatannol and enkephalin in donkey semen of HF group were significantly higher than those of LF group (P < 0.05), while the contents of taurocholic and lysophosphatidic acid were significantly lower than those of LF group (P < 0.05). The different metabolites were mainly related to sperm biological pathway response and oxidative stress. These metabolites may be considered as candidate biomarkers for different fertility in jacks.
... in improving sperm motility (Ahmadi, Bashiri, Ghadiri-Anari, &Nadjarzadeh, 2016;Balercia et al., 2004). The purpose of this quantitative assessment was to provide a critical evaluation of the effect of CoQ10 administration on semen parameters in infertile men. ...
Article
Coenzyme Q10 has shown promise in treating male infertility; however, there are inconsistencies across the published data. We undertook a quantitative meta‐analysis by pooling data from three placebo‐controlled randomised clinical trials (RCTs) in order to evaluate the efficacy of CoQ10 in improving semen parameters. Sperm count, sperm motility, sperm forward motility, sperm morphology and CoQ10 level in the seminal plasma were measured and quantitatively correlated with CoQ10 oral administration. Pooled analysis showed a significant impact of CoQ10 in improving sperm motility and forward motility, without a significant impact on sperm count, sperm morphology, ejaculate volume or seminal plasma level of CoQ10. Efficacy assessment suggested that CoQ10 shows better results at higher doses and when administered for a period of more than 3 months but not longer than 6 months. We conclude that CoQ10 has a profound effect on sperm motility and a meagre effect on all other parameters. Therefore, CoQ10 can be used for treating asthenozoospermic infertility with the dosage and duration depending upon the severity of the disorder and the patient's response to the treatment.
... This coenzyme enables for the electron transport in mitochondrial respiration and oxidative phosphorylation necessary for adenosine triphosphate (ATP) production (98). Although shown to be beneficial in treating male oligo-asthenospermia and in cardiology, the clinical use in POR is not abundant (98)(99)(100)(101). Preclinical studies in animals have suggested CoQ10 can protect ovarian reserve, possibly counteracting the physiological ovarian aging by restoring mitochondrial function and augmenting embryo cleavage and blastocyst generation (102)(103)(104). ...
Article
Full-text available
The infertile patients with aging ovaries—also sometimes referred to as impending premature ovarian insufficiency (POI), impending premature ovarian failure (POF), or poor ovarian responders (POR), constitute a significant and increasing bulk of the patients appealing to IVF/ART. Different causes have been cited in the literature, among the identified etiologies, including chromosomal and genetic etiology, metabolic, enzymatic, iatrogenic, toxic, autoimmune, and infectious causes. Although the most successful and ultimate treatment of POI/POF/POR patients is egg donation (ED), many, if not most, of these infertile women are reluctant to consent to ED upon the initial diagnostic interview, requesting alternative solutions despite the low odds for success. Despite anecdotal case reports, no unequivocal treatment proved to be successful for these patients in prospective randomized controlled trials. Nevertheless, the addition of growth hormone (GH) to ovarian stimulation in POR with GH deficiency may improve the results of controlled ovarian hyperstimulation (COH) and the IVF success. In patients with autoimmune etiology for POR/POI, the combination of glucocorticosteroids, pituitary-ovarian suppression, and COH may be successful in achieving the desired conception.
... Most commonly studied antioxidants were vitamin E, vitamin C, selenium, CoQ10, N-acetyl-cysteine, L-carnitine and zinc and their favourable effect was confirmed. On the other hand, some clinical trials in this review showed no significant improvement of semen morphology [10][11][12] or no response to treatment in 36.6% of the cases with Selenium and vitamin E [13] or even reported an adverse effect such as an increase of sperm decondensation with vitamins C and E, ß-carotene, zinc, and selenium [14]. ...
Article
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Background: The World Health Organization estimates that infertility concerns nearly 190 million people worldwide. Male associated factors are found up to 50% of the cases. This study aimed to investigate the effects of vitamin and antioxidant supplementation on semen parameters and pregnancy rates. Methods: We report a prospective study comparing sperm parameters before and after micronutrient treatment in 52 infertile male patients. The duration of the study was 15 months. The primary outcomes were the evolution of sperm parameters after treatment intake. The secondary outcomes were pregnancy rates. Wilcoxon Signed Rank test was used for statistical analysis. Results: The mean age was 36.2 years. Primary Infertility was reported in 35 cases (71.1%). Varicocele was reported in 12 patients (23%). Infertility remained idiopathic in 18 cases (34.6%). Before treatment, the mean sperm concentration was 39.3 106/ml (0.35-290). The mean progressive motility was 34.3 % (3-76%). The mean typical morphology was 3.6% (1-17%). After treatment, the mean sperm concentration was 39.6 106/ml (1.4-240); the mean progressive motility was 36.2% (7-78%); the mean typical morphology was 3.5% (1-13%). The main variations of the semen observed after treatment were an improvement of the sperm concentration in 55.8% and of the progressive motility in 51.9%. Sixteen pregnancies (30.7%) were obtained. Five pregnancies (9.6%) were spontaneous and 11 (21.1%) occurred after assisted reproductive techniques (3 after IVF-ICSI and 8 after intra uterine insemination). Conclusion: The results of this study are in favour of the positive effects of nutraceuticals and antioxidants on semen parameters and pregnancy rates.
... A randomized, double-blind, placebo-controlled trial of 212 men with idiopathic oligoasthenoteratospermia (OAT) who received CoQ10 (300 mg/day) for 26 weeks reported improvements in sperm concentration and motility post-therapy [29]. Balercia et al. [21,30], in two studies of 82 men with idiopathic asthenospermia treated with CoQ10 (200 mg/day) for 6 months, also confirmed higher sperm progressive and total motility and an increase in seminal CoQ10 level after treatment. Furthermore, our recent systematic review and another systematic review including three randomized clinical trials in infertile men who received CoQ10 therapy confirmed improvements in sperm concentration and motility in these men, although there was no increment in pregnancy rates [31,32]. ...
Article
Objective: Oxidative stress and sperm DNA fragmentation (SDF) have been linked to idiopathic male infertility (IMI). Various antioxidants have been tried to improve semen parameters and fertility potential in IMI patients, but with inconsistent results. The study aimed to compare the effects of coenzyme Q10 (CoQ10) and Centrum multivitamins on semen parameters, seminal antioxidant capacity, and SDF in infertile men with idiopathic oligoasthenospermia (OA). Methods: This prospective controlled clinical study involved 130 patients with idiopathic OA and 58 fertile controls. The patients were divided randomly into two groups: the first group received CoQ10 (200 mg/day orally) and the second group received Centrum multivitamins (1 tablet/day) for 3 months. Semen parameters, CoQ10 levels, reactive oxygen species (ROS), total antioxidant capacity (TAC), catalase, SDF, and serum hormone levels (follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin) were compared at baseline and after 3 months. Results: Both CoQ10 and Centrum improved sperm concentration and motility, but the improvement was greater with Centrum therapy (p<0.05). Similarly, both therapies improved antioxidant capacity, but TAC and catalase improvement was greater (p<0.01 and p<0.001 respectively) with CoQ10, whereas ROS (p<0.01) and SDF (p<0.001) improvements were greater with Centrum administration. Centrum therapy was associated with reduced serum testosterone (p<0.05). Conclusion: In conclusion, both CoQ10 and Centrum were effective in improving semen parameters, antioxidant capacity, and SDF, but the improvement was greater with Centrum than with CoQ10. Therefore, Centrum-as a source of combined antioxidants-may provide more effective results than individual antioxidants such as CoQ10 in the treatment of infertile men with idiopathic OA.
... Further, a randomized double-blind placebo-controlled study observed an increase in forward and total motility after 6 months of CoQ10 treatment (Balercia, 2004), which may suggest that a longer treatment regimen may be more effective in improving sperm pa- (Dubeux et al., 2016). Correlation of pregnancy rate with semen parameters and antioxidant capacity have been reported previously as well as an increase in pregnancy rate following antioxidant treatment in infertile men (Huang et al., 2018). ...
Article
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Different antioxidants including coenzyme Q10 (CoQ10) have been tried to treat idiopathic male infertility (IMI) with variable results. Therefore, this study aimed to determine the clinical and biochemical predictors of pregnancy outcome and time to pregnancy (TTP) in infertile men with idiopathic oligoasthenospermia (OA) pre‐ and post‐CoQ10 therapy. This prospective controlled clinical study included 178 male patients with idiopathic OA and 84 fertile men (controls). Patients received 200 mg of oral CoQ10 once daily for 6 months. Demographics, semen parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), catalase (CAT), glutathione peroxidase (GPx), sperm DNA fragmentation (SDF) and body mass index were measured and compared at baseline and after 6 months. All participants were followed up for another 18 months for pregnancy outcome and TTP. CoQ10 therapy for 6 months significantly improved semen parameters, antioxidant measures and reduced SDF. The pregnancy rate was 24.2% and TTP was 20.52 ± 6.72 months in patients as compared to 95.2% and 5.73 ± 6.65 months in fertile controls. After CoQ10 therapy, CoQ10 level, sperm concentration, motility and ROS were independent predictors of pregnancy outcome and CoQ10 level, male age, sperm concentration, motility, ROS and GPx were independent predictors of TTP in patients. In conclusion, CoQ10 therapy of 6 months is a potential treatment for men with idiopathic OA. CoQ10 level, male age, semen parameters, ROS and GPx could potentially be used as diagnostic biomarkers for male fertility and predictors for pregnancy outcome and TTP in these patients.
... In addition, Tavilani found that the content of lipid peroxidation product malondialdehyde (MDA) in sperm of asthenospermia men was significantly higher and negatively correlated with PC [27]. Reduced PC content can affect the antioxidant enzyme system in sperm and further lead to reduced sperm motility, which may be a potential mechanism of asthenospermia [28,29]. Another previous study of the bull semen metabolome also revealed that one metabolite that accumulated in the sperm of HF bulls was lysophosphatidylcholine (LPC 16:0), a lysophospholipid with a chain of palmitic acid at the C-1 position. ...
Article
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The cryopreservation technology of sperm has promoted the popularization of artificial insemination in the reproductive process of donkeys to a certain extent, but the freezing-thawing process would bring damage to the sperm, and the vitality of the sperm would be greatly reduced after freezing. Sperm metabolites play an important role in the process of sperm freezing, and also have an important impact on the vitality and fertilization rate of sperm after freezing-thawing. In this study, the LC-MS/MS analysis method was used to compare the metabolic profiles of high freezability (HF) and low freezability (LF) male donkey sperm after freezing-thawing. We identified 1323 metabolites in total, of which 17 metabolites are significantly different between the two groups. Most of these metabolites belong to fatty acids and phospholipids, including phosphatidylcholine, stearic acid and so on. These different metabolites are mostly related to the plasma membrane fatty acids of sperm and oxidative stress. Our results illustrate several metabolites related to sperm freezability and provide corresponding biomarkers.
... CoQ10 is an intermediate of the mitochondrial electron transport chain [153,154]. Low seminal plasma/sperm concentrations of CoQ10 have been associated with reduced sperm motility [155]. ...
Chapter
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Within the male reproductive system, oxidative stress (OS) has been identified as prevailing etiology of male infertility. The effects of reactive oxygen species (ROS) on male fertility depend on the dimensions, “modus operandi” of the ROS and the oxido-reduction potential (ORP) of the male reproductive tract. Hereupon, for an adequate response to OS, the cells of our body are endowed with a well-sophisticated system of defense in order to be protected. Various antioxidant enzymes and small molecular free radical scavengers, maintain the delicate balance between oxidants and reductants (antioxidants), crucial to cellular function and fertility. Therapeutic use of antioxidants is an optimal and coherent option in terms of mitigating OS and improving semen parameters. Therefore, recognizing and managing OS through either decreasing ROS levels or by increasing antioxidant force, appear to be a requesting approach in the management of male infertility. However, a clear defined attitude of the experts about the clinical efficacy of antioxidant therapy is still deprived. Prominently, antioxidant such as coenzyme Q10, vitamin C and E, lycopene, carnitine, zinc and selenium have been found useful in controlling the balance between ROS production and scavenging activities. In spite of that, healthy lifestyle, without smoke and alcohol, everyday exercise, reduction of psychological stress and quality well-designed meals, are habits that can overturn male infertility.
... Oxidative stress (OS) and reactive oxygen species (ROS) are considered damaging to sperm and are responsible for 30%-80% of cases of subfertility [7]. OS, caused by the disruption of the prooxidant-antioxidant balance [8], affects male fertility and sperm function [9][10][11][12]. ...
Article
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Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.
... Previous reports have shown that oral intake of CoQ10 increases its level in various tissues including muscle, adrenal gland, sperm and ovaries. Furthermore, CoQ10 is also present in human follicular fluid, which suggests it might act as antioxidant in the human reproductive system [12][13][14]. In fact, several recent studies have shown that CoQ10 can improve mitochondrial function and rescue ovarian aging by protecting ovarian reserve against oxidative damage [15][16][17]. ...
Article
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Background: Several studies have shown that coenzyme Q10 (CoQ10) can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility due to ovarian aging. However, few studies have examined the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs and recovers ovarian function in a 4-vinylcyclohexene diepoxide (VCD)-induced mouse model of ovarian failure. Methods: Forty female C57BL/6 mice aged 6 weeks were randomly divided into four groups (n = 10/group): a control group administered saline orally, a CoQ10 group administered 150 mg/kg/day of CoQ10 orally in 1 mL of saline daily for 14 days, a VCD group administered 160 mg/kg/day of VCD i.p. in 2.5 mL of saline/kg for 5 days, and a VCD + CoQ10 group administered VCD i.p. for 5 days injection and CoQ10 (150 mg/kg/day) orally for 14 days. After treatment, follicle counts were evaluated by hematoxylin and eosin (H&E) staining, and ovarian mRNA expressions of Bmp-15, Gdf-9, and c-Kit were examined by quantitative real-time PCR. Serum FSH, AMH, and ROS levels were also measured. Oocyte-like structure counts and the expressions of Oct-4 and MVH were also evaluated after culturing OSE for 3 weeks. In a second experiment, 32 female mice were administered CoQ10 as described above, induced to superovulate using PMSG and hCG, and mated. Numbers of zygotes and embryo development rate were examined. Results: Postcultured OSE showed significant increases in the numbers of oocyte-like structure and that the expression of Oct-4 and MVH were higher in the VCD + CoQ10 group than in the VCD group (p < 0.05). Numbers of surviving follicles from primordial to antral follicles, numbers of zygotes retrieved and embryo development rate to blastocyst were significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.01). Serum AMH level and ovarian expressions of Bmp-15, Gdf-9 and c-Kit were also significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.05). In contrast, serum ROS level was significantly lower in the VCD + CoQ10 group than in the VCD group (p < 0.05). Conclusion: This study shows that CoQ10 stimulates the differentiation of OSE-derived OSCs and confirms that CoQ10 can reduce ROS levels and improve ovarian function and oocyte quality in mice with VCD-induced ovarian failure.
... Deficiencies in CoQ10 synthesis are associated with certain clinical disorders related to high energy-consuming tissues, including skeletal muscles, endocrine glands, and the nervous system [12]. Studies have demonstrated that CoQ10 supplementation causes a significant increase of CoQ10 levels in some tissues, such as muscle, sperm, and plasma, as well as a remarkable increase in the adrenal glands and ovaries [13][14][15][16]. Therefore, the supplementation of CoQ10 protects cells against ROS-induced damage due to its antioxidant properties, which strengthen endogenous cellular antioxidant systems. ...
Article
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Purpose We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage. Methods Twenty-four adult female Sprague–Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed. Result(s) The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03). Conclusion(s) CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.
... Previous literature has shown that oral intake of CoQ10 notably brings up its level in various tissues including muscle, adrenal gland, sperm and ovaries. Moreover, it is observed in the human follicular uid, suggesting its possible function of antioxidant protection in the human reproductive system [12][13][14]. Several studies have recently shown that CoQ10 can improve mitochondrial function and rescue ovarian aging by protecting ovarian reserve against oxidative damage [15][16][17]. ...
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Background: Several studies have shown that CoQ10 can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility with ovarian aging. However, there are few studies the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs while recovering ovarian function using 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure mouse model. Methods: C57BL/6 female mice aged 6 weeks were randomly divided into four groups (n=10/group): (Control) saline and orally, (CoQ10) 150 mg/kg/day orally in 1 mL of saline daily for 14 days, (VCD) 160 mg/kg/day, 2.5 ml/kg ip for 5 days, (VCD+CoQ10) 5 days after VCD injection, CoQ10 (150 mg/kg/day) orally for 14 days. After final treatment of CoQ10, follicle counts were evaluated by hematoxylin and eosin (H&E) staining, and ovarian mRNA expressions of Bmp-15, Gdf-9, and c-Kit were examined by quantitative real-time PCR. Serum FSH, AMH, and ROS levels were also measured. Oocyte-like structure count and expression of Oct-4 and MVH were evaluated from postcultured OSE for 3 weeks. In the second experiment, another 32 female mice were administered with CoQ10 in the same way as above and were superovulated by PMSG and hCG, followed by mated with males. Then, numbers of zygotes ovulated and embryo development rate were examined. Results: Postcultured OSE had significantly increased numbers of oocyte-like structure and expression of Oct-4 and MVH in VCD+CoQ10 group compared to VCD group (p <0.05). Numbers of surviving follicles including from primordial to antral follicles, numbers of zygotes retrieved and embryo development rate to blastocyst were significantly higher in VCD+CoQ10 group compared to VCD group (p <0.01). Serum AMH level and ovarian expression of Bmp-15, Gdf-9, and c-Kit were significantly increased in VCD+CoQ10 group compared to VCD group (p <0.05). In contrast, serum ROS level was significantly decreased in VCD+CoQ10 group compared to VCD group (p <0.05). Conclusion(s): This is the first study to show that CoQ10 stimulates the differentiation of OSE-derived OSCs. Also this study confirms that CoQ10 can reduce ROS levels, leading to improve ovarian function and oocyte quality in ovarian failure mice.
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Background: Infertility is defined as failure in fertility after having sex for at least one year, if no contraceptive method is used, and 15% of the world's population is involved, of which 20-70 percent is related to men. Studies show that infertility is associated with a decrease in Q10 levels in the serum and seminal fluid, and its supplementation can reduce the symptoms of infertility, and improve it as well. Methods: The purpose of this study was to review the research done to investigate the relationship between Q10 and infertility. Clinical trial studies on the effect of supplementation of Q10 on male infertility from PubMed, Scopus, ISI, and Google Scholar databases between 2000 and 2017 were assessed using the keywords of coenzyme Q10, ubiquinol-10, infertility, male infertility, male fertility problems, semen parameters, sexual dysfunction. Findings: In most clinical trial studies, supplementation of Q10 had a positive effect on sperm parameters such as concentration, morphology, and movement. DNA fragmentation was also reduced; moreover, antioxidant enzymes of catalase and superoxide dismutase as well as total antioxidant capacity were significantly higher than before the intervention. However, some studies found no significant effect of Q10 on the sperm parameters. Conclusion: In most studies, the positive effects of Q10 supplement on sperm parameters, DNA damage, antioxidant capacity, and antioxidant enzymes have been proven, but due to the lack of studies, more clinical trial studies are needed in this area.
Article
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It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants could have a significant role in the treatment of male infertility. The main objectives of this study are: 1) to systematically review the current evidence for the utility of antioxidants in the treatment of male infertility; and 2) propose evidence-based clinical guidelines for the use of antioxidants in the treatment of male infertility. A systematic review of the available clinical evidence was performed, with articles published on Scopus being manually screened. Data extracted included the type of antioxidant used, the clinical conditions under investigation, the evaluation of semen parameters and reproductive outcomes. The adherence to the Cambridge Quality Checklist, Cochrane Risk of Bias for randomized controlled trials (RCTs), CONSORT guidelines and JADAD score were analyzed for each included study. Further, we provided a Strength Weakness Opportunity Threat (SWOT) analysis to analyze the current and future value of antioxidants in male infertility. Of the 1,978 articles identified, 97 articles were included in the study. Of these, 52 (53.6%) were uncontrolled (open label), 12 (12.4%) unblinded RCTs, and 33 (34.0%) blinded RCTs, whereas 44 (45.4%) articles tested individual antioxidants, 31 (32.0%) a combination of several products in variable dosages, and 22 (22.6%) registered antioxidant products. Based on the published evidence, we 1) critically examined the necessity of additional double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for antioxidant therapy in male infertility. The current systematic review on antioxidants and male infertility clearly shows that antioxidant supplementation improves semen parameters. In addition, it provides the indications for antioxidant treatment in specific clinical conditions, including varicocele, unexplained and idiopathic male infertility, as well as in cases of altered semen quality.
Chapter
Coenzyme Q10 (CoQ10) intake and supplementation has been directly and indirectly associated with physiological function relative to exercise, aging and reproduction. This chapter describes several significant aspects regarding biochemical properties and mechanism of action of CoQ10 in male and female fertility and reproduction. This effect is mainly through its action as an antioxidant, protecting against oxidative stress by controlling the levels of reactive oxygen species (ROS) associated with reproductive pathologies. Although some studies support the evidence of use of CoQ10 to improve fertility, the available literature is contradictory and conflicting due to lack of standardization regarding type, dosage and time frame of treatment with CoQ10 as well as the bio-specimen, the exercise protocol employed and the assays used to analyze these specimens. However, CoQ10 supplementation seems to be able to improve both male and female gamete physiology, conception and embryo development and pregnancy success, something that may be related to the protecting effect against ROS-related fertility issues. It seems it may, as well, attenuate somewhat the negative impact of age on fertility, though discontinuation of treatment will result in cessation or diminution of such effect.
Book
This book focuses on the use of various molecules with antioxidant properties in the treatment of major male genital tract disorders, especially male infertility, erectile dysfunction, and accessory gland infection. The coverage also includes discussion of pathophysiology, the molecular basis of male infertility, and the rationale for use of antioxidants, with particular attention to coenzyme Q10 and carnitine. Oxidative stress occurs when the production of reactive oxygen species, including free radicals, exceeds the body’s natural antioxidant defences, leading to cellular damage. Oxidative stress is present in about half of all infertile men, and reactive oxygen species can produce infertility both by damaging the sperm membrane, with consequences for sperm motility, and by altering the sperm DNA. There is consequently a clear rationale for the use of antioxidant treatments within andrology, and various in vitro and in vivo studies have indicated that many antioxidants indeed have beneficial impacts. In providing a detailed and up-to-date overview of the subject, this book will be of interest to both practitioners and researchers in andrology, endocrinology, and urology.
Chapter
Even if varicocele is considered as one of the first known causes of male infertility, to date, it is still under debate if varicocele repair is able to improve fertility.
Article
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The male factor is responsible for infertility in about 35–40% of all cases. Idiopathic oligo- and/or astheno- and/or therato-zoospermia is one of the most common male fertility disorders and remains a significant therapeutic challenge. The primary cause of idiopathic male infertility remains unknown but seems to be associated with oxidative stress. Objective: The use of antioxidative formulation to improve qualitative and quantitative deficiencies in the male gametes. In total, 78 subjects were treated with a combination of 1,725 mg L-carnitine fumarate, 500 mg acetyl-L-carnitine, 90 mg vitamin C, 20 mg coenzyme Q 10 , 10 mg zinc, 200 µg folic acid, 50 µg selenium, and 1.5 µg vitamin B 12 (Proxeed ® Plus, Sigma-Tau, Italy) for 6 months; the preparation was taken twice daily from the time idiopathic infertility was diagnosed. Basic seminal parameters were evaluated by a European Society of Human Reproduction and Embryology (ESHRE) -certified embryologist following the fifth edition of the World Health Organisation (2010) guidelines at three time points: at baseline and 3 and 6 months of treatment. Improvements in semen parameters (differing in terms of dynamics) were evident at 3 months and gradually improved over the 6 months of treatment. Each parameter: sperm concentration, total sperm count, sperm total and progressive motility improved significantly after treatment except for the percentage of sperm of abnormal morphology and ejaculate volume. Proxeed Plus was effective for patients with idiopathic infertility; however, a long treatment period is needed to achieve optimal results.
Article
Although coenzyme Q10 (CoQ10) serves as an antioxidant and energy source for spermatozoa when added to stallion semen before cooling or freezing, the effects of feeding CoQ10 on semen quality have not been studied. We assessed the effects of daily oral ingestion of CoQ10-ubiquinol by stallions on their plasma CoQ10 concentrations and semen quality. Seven mature Andalusian stallions ate 1g ubiquinol/day for 4 weeks followed by a 4-week washout period. Four horses initially completed an additional 4-week control period without ubiquinol. Blood was sampled weekly for determination of plasma CoQ10 concentrations. Ejaculates were collected every two weeks and assessed for total motility (TM), progressive motility (PM), and viability (V) after cooling for 24hours (T1), immediate cryopreservation (T2), and cryopreservation after 24hours cooling (T3). Ingesting ubiquinol resulted in an increase in plasma CoQ10 concentration (P < .001). Two weeks of CoQ10-ubiquinol resulted in improved V with all treatments (T1: P = .007; T2: P = .05; T3: P = .01) and PM with T3 (P = .04). In five stallions, TM and PM were also improved for T1 (P = .01 and P = .02, respectively) and TM increased with T2 (P = .03). Overall, semen quality parameters increased within the first 2 weeks of supplementation, plateaued at the end of the 4-week supplementation period and persisted after discontinuing ubiquinol until the end of the sampling period (8 weeks). Feeding 1 g CoQ10-ubiquinol for 4 weeks to breeding stallions improved semen quality after cooling and freezing in 5 of 7 stallions. This could be important for improving reproductive efficiency in stallions.
Chapter
This chapter deals with the role of coenzyme Q10 in male infertility in the light of the increasing evidence of oxidative damage and antioxidant defence in sperm cells and seminal plasma. Reactive oxygen species have a key pathogenetic role in male infertility as well as a well-recognized physiological function. The involvement of coenzyme Q10 in mitochondrial bioenergetics and its antioxidant properties are at the basis of its role in seminal fluid. Therefore, in this chapter, we present the physiopathological basis linking coenzyme Q10 and its therapeutical properties. In addition, we provide an updated discussion of the clinical studies assessing the therapeutical effects of coenzyme Q10.
Article
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Coenzyme Q10 plays a vital role in cellular energy production and with its antioxidant activity can increase the body's immune system. This coenzyme has the highest density in tissues with high energy turnover such as the heart, brain, liver and kidney. Reports suggest that coenzyme Q10 is effective in improves Exercise performance, Reducing Exercise-Induced Muscular Injury, Hypertension, Cardiac Failure, interact with statins, endothelial function, interactions with extracellular superoxide dismutase, Sperm motility, migraine and Parkinson's disease. Also this coenzyme is effective in other diseases such as AIDS, burns, cancer, drug addiction, dyspepsia, multiple organs failure, surgery infection, chronic fatigue syndrome, autism and other known cognitive disorders. The role of coenzyme Q10 also have been proven in the treatment of periodontal disease, gastric ulceration, obesity, muscular dystrophy and allergy. Also, coenzyme Q10 supplement has good effects on patients with diabetes and deafness. According to the aforementioned benefits, coenzyme Q10 supplementation is recommended for the prevention and treatment of many other diseases that people are not able to produce enough coenzyme Q10
Chapter
Many causes of male infertility are unknown, and for this reason, numerous studies have been carried out, analyzing gene expression, epigenetics modifications, and mostly the role of reactive oxygen species (ROS) and antioxidants. It is well recognized that oxidative stress is a cause of male infertility, but the use of antioxidants as a treatment is still debated, and it is considered as a supportive therapy, rather than etiological or physiopathological, on the real effect of oral supplementation. Oxidative stress is determined when there is an imbalance between the production of ROS and the neutralizing activity of antioxidant system. It leads to a pathological and often irremediable cell damage. In particular spermatozoa are very susceptible to oxygen effects because their membranes are rich in polyunsaturated fatty acids that assure fluidity and flexibility; this one makes spermatozoa more vulnerable to lipid peroxidation.
Article
"Cyclophosphamide is an anticancer drug that acts as an alkylating agent after metabolism in the liver. Despite its many clinical applications in cancer treatment, this drug has toxic effects on the body's organs, especially the genitals. One of the most critical side effects is a change in the function of the female reproductive system, which can lead to infertility. This study aimed to investigate the antioxidant effects of coenzyme Q10 on cyclophosphamide-induced toxicity in vitro fertilized embryos in mice. In this experimental study, 24 female mice weighing 25 g 4 groups of 6 were divided and treated for 21 days. The first group (control group), solvent (cyclophosphamide) including DMSO and PBS (0.1 ml intraperitoneally), the second group (sham group), cyclophosphamide at a dose of 10 mg/kg was injected as a single dose, and the third group (experimental group), along with single-dose cyclophosphamide, coenzyme Q10 at a dose of 200 mg/kg/day was injected intraperitoneally and the fourth group (positive control group), only coenzyme Q10 at a dose of 200 mg/kg/day was injected intraperitoneally. At the end of the treatment period, ovulation stimulation was performed using PMSG and HCG hormones. Six adult male mice were used to prepare normal sperm. The animals were facilitated after anesthesia. After extraction of regular eggs and sperm and fertilization in HTF + 4 mg BSA medium, the fertilized eggs were incubated for 120 hours, and the embryonic developmental stages were examined during this period. Were analyzed by ANOVA and comparison of ratios. Cyclophosphamide significantly reduced oocyte quality, fertilization rate, pre-implantation embryonic development, and embryo quality. Coenzyme Q10 (Co Q10) significantly reduced the adverse effects of cyclophosphamide. The present study showed that crocin could protect the fertility of the female sex against damage caused by cyclophosphamide. "
Article
Oxidative stress owing to an imbalance between reactive oxygen species and antioxidants, such as coenzyme Q10 (CoQ10), is a major contributor to male infertility. We investigated the effects of the reduced form of CoQ10 (ubiquinol) supplementation on semen quality in dogs with poor semen quality. Three dogs received 100 mg of ubiquinol orally once daily for 12 weeks. Semen quality, serum testosterone, and seminal plasma superoxide dismutase (SOD) activity were examined at 2-week intervals from 2 weeks before ubiquinol supplementation to 4 weeks after the treatment. Ubiquinol improved sperm motility, reduced morphologically abnormal sperm, and increased seminal plasma SOD activity; however, it had no effect on testosterone level, semen volume, and sperm number. Ubiquinol supplementation could be used as a non-endocrine therapy for infertile dogs.
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The temporal disappearance of natural antioxidants associated with human low density lipoprotein (LDL) in relation to the appearance of various classes of lipid hydroperoxides was investigated under three types of oxidizing conditions. Freshly isolated LDL from plasma of healthy subjects was free of detectable amounts of lipid hydroperoxides as measured by HPLC postcolumn chemiluminescence detection. Exposure of such LDL to a mild, constant flux of aqueous peroxyl radicals led to rapid and complete oxidation of ubiquinol-10, followed by slower partial depletion of lycopene, beta-carotene, and alpha-tocopherol. After an initial lag period of complete inhibition of detectable lipid peroxidation, formation of hydroperoxides of cholesterol esters, triglycerides, and phospholipids was observed. The onset of detectable lipid peroxidation corresponded closely with the completion of ubiquinol-10 consumption. However, small amounts of ascorbate, present as a contaminant in the LDL preparation, rather than ubiquinol-10 itself were responsible for the initial lag period. Thus, complete consumption of ubiquinol-10 was preceded by that of ascorbate, and exposure of ascorbate-free LDL to aqueous peroxyl radicals resulted in immediate formation of detectable amounts of lipid hydroperoxides. The rate of radical-mediated formation of lipid hydroperoxides in ascorbate-free LDL was low as long as ubiquinol-10 was present, but increased rapidly after its consumption, even though more than 80% and 95% of endogenous carotenoids and alpha-tocopherol, respectively, were still present. Qualitatively similar results were obtained when peroxyl radicals were generated within LDL or when the lipoprotein was exposed to oxidants produced by activated human polymorphonuclear leukocytes. LDL oxidation was reduced significantly by supplementing the lipoprotein preparation with physiological amounts of either ascorbate or ubiquinol-10. Our data show that ubiquinol-10 is much more efficient in inhibiting LDL oxidation than either lycopene, beta-carotene, or alpha-tocopherol.
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The properties and distribution of nonaprenyl-4-hydroxybenzoate transferase in rat liver were investigated with subcellular fractions, liver perfusion, and in vivo labeling with [3H]solanesyl-PP. In addition to some ubiquinone-9, only one labeled intermediate, i.e. nonaprenyl-4-hydroxybenzoate, was obtained. In the total microsomal fraction, the enzyme had a pH optimum of 7.5 and was completely inhibited by Triton X-100 and deoxycholate, but not by taurodeoxycholate and beta-octyl glucoside. Liver, kidney, and spleen demonstrated the highest activities of nonaprenyl-4-hydroxybenzoate transferase. Upon subcellular fractionation, high specific activities were found in smooth II microsomes and Golgi III vesicles. The enzyme was also found in lysosomes and plasma membranes, but only at low levels in rough and smooth I microsomes and mitochondria and not at all in peroxisomes and cytosol. When the product of the transferase reaction was used as a substrate in vitro and in a perfusion system, the only product obtained was end product ubiquinone-9. Although the transferase reaction was associated with the inner, luminal surface of microsomal vesicles, the terminal reaction(s) for ubiquinone-9 synthesis are found at the outer cytoplasmic surface. The results suggest that the major site for ubiquinone synthesis is the endoplasmic reticulum-Golgi system, which also participates in the distribution of ubiquinone-9 to other cellular membranes.
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Addition of the divalent cation ionophore, A23187, to washed populations of human spermatozoa resulted in a sudden burst of production of reactive oxygen species which peaked within 3-5 min. This activity was dependent upon the presence of calcium in the external medium and was unaffected by the mitochondrial inhibitors, oligomycin, antimycin and rotenone. Studies with scavengers of reactive oxygen species revealed that, while reagents directed against singlet oxygen and the hydroxyl radical were without effect, cytochrome C reduced the response to A23187 by about 50%, suggesting that the superoxide anion radical is a major product of the activated human spermatozoon. The clinical implications of these studies stem from the considerable variation observed between individuals in the levels of reactive oxygen species produced by the spermatozoa. This variability was shown to be inversely related to the ability of the spermatozoa to exhibit sperm-oocyte fusion on exposure to A23187; defective samples exhibited a basal level of reactive oxygen species production which was 40 times that observed with normal functional cells.
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Rabbit spermatozoa released from the cauda epididymidis into Tris phosphate medium containing KCl or NaCl and 0.4 mM EDTA underwent spontaneous lipid peroxidation during aerobic incubation at 37 degrees C. In the medium containing 130 mM K+ and O mM Na+ (KTP), the rate of lipid peroxidation, as measured by malonaldehyde production, proceeded at a linear rate of 0.045 nmol malonaldehyde/h per 10(8) cells for 22 h. The motility of these spermatozoa declined with time in medium KTP, with 40% initial forward motility decreasing to zero in 4 h and initial 60% flagellar beating ceasing after 12 h. The percent inert spermatozoa showing no flagellar motion in KTP increased linearly with production of malonaldehyde; all flagellar activity stopped at 0.5 nmol malonaldehyde/10(8) cells. In the Tris phosphate medium containing 120 mM Na+ and 10 mM K+ (NTP), the percentage of sperm showing forward motility was close to 100% and this declined to 60% after 16 h aerobic incubation. Flagellar beating was not observed. In medium NTP, the rate of lipid peroxidation was 0.0056 nmol malonaldehyde/h per 10(8) cells, eightfold lower than that observed in KTP. The same linear correlation between malonaldehyde production and percent inert sperm was found as for KTP: 0.5 nmol malonaldehyde/10(8) cells also corresponded to cessation of flagellar motion. The dependence of motility maintenance on K+ concentration in Tris phosphate medium containing (Na+ + K+)=130 mM showed maximal maintenance at 10 mM K+, with a decline at 0 mM K+ and steep decline at K+ concentrations greater than 30 mM. This strong dependence of rabbit sperm peroxidation on ionic composition of the medium is suggested to involve perturbation of the equilibrium between O2 .- and its conjugate acid species being the agent of peroxidation.
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The aim of our study was to investigate the relationships between the levels of coenzyme Q10 (CoQ10) and vitamin E and the levels of hydroperoxide in three subfractions of low density lipoproteins (LDL) that were isolated from healthy donors. LDL3, the densest of the three subfractions, has shown statistically significant lower levels of CoQ10 and vitamin E, which were associated with higher hydroperoxide levels when compared with the lighter counterparts. After CoQ10 supplementation, all three LDL subfractions had significantly increased CoQ10 levels. In particular, LDL3 showed the highest CoQ10 increase when compared with LDL1 and LDL2 and was associated with a significant decrease in hydroperoxide level. These results support the hypothesis that the CoQ10 endowment in subfractions of LDL affects their oxidizability, and they have important implications for the treatment of disease.
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The aim of the study described here was to evaluate any possible effect of L-carnitine on spermatozoal motility in a group of patients with unexplained asthenozoospermia in four different infertility centres. One hundred patients received 3 g d-1 of oral L-carnitine for 4 months. Sperm parameters were studied before, during and after this treatment. Motility was also studied by means of a computer-assisted sperm analysis. The results of the study indicate that L-carnitine is able to increase spermatozoal motility, both in a quantitative and in a qualitative manner (per cent motile spermatozoa increased from 26.9 +/- 1.1% to 37.7 +/- 1.1% [P < 0.001]; per cent spermatozoa with rapid linear progression increased from 10.8 +/- 0.6% to 18.0 +/- 0.9% [P < 0.001]; mean velocity increased from 28.4 +/- 0.6 microns s-1 to 32.5 +/- 0.8 microns s-1 [P < 0.001]; linearity index increased from 3.7 +/- 0.1 to 4.1 +/- 0.1 [P < 0.001], especially in the subgroup of patients with poor rapid linear progression of spermatozoa (per cent of motile spermatozoa increased from 19.3 +/- 1.9% to 40.9 +/- 1.4% [P < 0.001], and per cent of spermatozoa with rapid linear progression increased from 3.1 +/- 0.4% to 20.3 +/- 1.6% [P < 0.001]) An increase in spermatozoal output was also observed (total number of ejaculated spermatozoa increased from 142.4 +/- 10.3 10(6) to 163.3 +/- 11.0 x 10(6) [P < 0.001]). The authors conclude that oral administration of L-carnitine may improve sperm quality at least in patients with idiopathic asthenozoospermia.
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In an attempt to establish the relative importance of diffusional and chemical control in the reactivity of the two of the two substrates, ubiquinol and cytochrome c, we have undertaken as extensive characterization of the steady-state kinetics of ubiquinol-cytochrome c reductase (EC 1.10.2.2) when present in open submitochondrial particles from bovine heart. The kinetic pattern follows a Ping Pong mechanism; contrary to the situation found with the isolated enzyme [Speck and Margoliash (1984) J. Biol. Chem. 259, 1064-1072, and confirmed in our laboratory], no substrate inhibition by oxidized cytochrome c was observed with the membrane-bound enzyme. Endogenous oxidized ubiquinone-10 is unable to exert product inhibition under the conditions employed. In the Ping Pong mechanism for this enzyme, the reaction scheme can be clearly divided into two parts, and the Kmin. (kcat./km) value for one substrate is independent of the rate constant for the second substrate. Both ubiquinol-1 and ubiquinol-2 can be used as electron donors reacting with the enzyme from within the lipid bilayer [Fato, Castelluccio, Palmer and Lenaz (1988) Biochim. Biophys. Acta 932, 216-222]; the kmin. values for ubiquinols, when calculated on the basis of their membranous concentrations, are significantly lower than the kmin. for cytochrome c. The temperature-dependence of the kinetic parameters was investigated by titrating each of the substrates under quasi-saturating concentrations of the second substrate. Arrhenius plots of Vmax. extrapolated from both cytochrome c and ubiquinol titrations were linear, when care was taken to verify the quasi-saturating concentrations of the fixed co-substrate. The Arrhenius plots for the kmin. values for both ubiquinol and cytochrome c were linear, but the activation energy was much higher for the former, particularly when calculated for ubiquinol dissolved in the lipid phase; the very low value of activation energy of the kmin. for cytochrome c is strong support for diffusion control being present in the reaction of cytochrome c with the membranous enzyme. In contrast to the soluble enzyme, ubiquinone titrations of submitochondrial particles at low cytochrome c concentrations deviated from hyperbolic behaviour. Changing the medium viscosity with either poly(ethylene glycol) or sucrose had a strong effect on the cytochrome c kmin., whereas the change in the ubiquinol kmin. was much smaller. From the viscosity studies the extent of diffusional control could be calculated, revealing that the reaction with cytochrome c was mostly diffusion-limited. The viscosity of the membrane was changed by incorporating cholesterol; no significant effect on the ubiquinol kmin. ascribable to diffusion control could be recognized.(ABSTRACT TRUNCATED AT 400 WORDS)
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There are several mechanisms acting in synergism that can impair sperm characteristics of patients with accessory gland infection. In some cases, conventional sperm variables are disturbed with oligo and/or asthenozoospermia. In other patients, these sperm variables may appear normal, but the functional capacity of spermatozoa may be impaired. In particular, changes in the composition of the sperm membrane may result in reduced acrosome reactivity and capacity to fuse with the oolemma, and oxidative damage of the sperm DNA may induce mutagenesis. Changes in the biochemical make-up of seminal plasma can also reduce the in-vivo fertilizing capacity of spermatozoa, and infection-related disruption of the blood-testis barrier can induce the generation of anti-sperm antibodies and immunological infertility. Many of these functional abnormalities will not become evident upon 'basic semen analysis', which explains why some authors are unable to link infection of the accessory sex glands to subfertility. Also, functional and anatomical damage acquired as a result of infection is often permanent and not reversible by (antibiotic) treatment. Clearly, there are many more aspects of male accessory gland infection that require investigation. Available data should stimulate clinicians to place more emphasis on the prevention of infection-related infertility than on its treatment, as the latter is often unsuccessful.
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Recent advances in understanding of male infertility have implicated two major causative factors, oxidative stress and Y chromosome deletions. A major cause of oxidative stress appears to be the high rate of reactive oxygen species generation associated with the retention of excess residual cytoplasm in the sperm midpiece. Other possible causes include the redox cycling of xenobiotics, and antioxidant depletion or apoptosis. Oxidative stress induces peroxidative damage in the sperm plasma membrane and DNA damage in both the mitochondrial and nuclear genomes. Nuclear DNA damage in the germ line of the father may be associated with pathology in the offspring, including childhood cancer and infertility. Gene deletions on the non-recombining region of the Y chromosome account for the infertility observed in about 15% of patients with azoospermia and 5-10% of subjects with severe oligozoospermia. The Y chromosome is particularly susceptible to gene deletions because of the inability of the haploid genome to deploy recombination repair in retrieving lost genetic information. Aberrant recombination, defective chromatin packaging, abortive apoptosis and oxidative stress may all be involved in the aetiology of DNA damage in the germ line. The factors responsible for Y chromosome deletions in spermatozoa remain unresolved but may be one facet of a central reproductive problem: controlling the amount of oxidative stress experienced by germ cells during their differentiation and maturation in the male reproductive tract.
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We have undertaken a prospective analysis of the diagnostic significance of three different criteria of human sperm function including the conventional semen profile, measurements of hamster-oocyte fusion, and determinations of reactive oxygen species generation in 139 couples. The latter, who were characterized by a lack of detectable abnormalities in the female partner, were followed up for a maximum of 4 years to determine the incidence of spontaneous pregnancy in the absence of therapeutic intervention. Assessments of monthly fecundity with life table analysis techniques revealed a highly significant, positive relationship between fertility and hamster-oocyte fusion rates that were measured in the presence of the ionophore, A23187. Conversely, reactive oxygen species generation was shown to be negatively associated with both the outcome of the sperm-oocyte fusion assay and fertility in vivo. The clinical significance of these diagnostic techniques was emphasized by the fact that within the same data set, the conventional semen profile was of no significant diagnostic value.
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Coenzyme Q10 (CoQ10) levels were assayed in total seminal fluid or both in seminal fluid and seminal plasma in 77 subjects with normal or pathological findings at standard semen analysis. CoQ10 levels showed a significant correlation with sperm count and with sperm motility. An interesting exception was constituted by patients with varicocele, in whom the correlation with sperm concentration was preserved, whereas the correlation with sperm motility was lacking. Moreover, they showed an increased ratio of plasma CoQ to total seminal CoQ10 in comparison with the other subjects. These data suggest a pathophysiological meaning of CoQ10 in human seminal fluid and a possible molecular defect in varicocele patients. CoQ10 measurement could represent an important examination in infertile patients; moreover, from these results a rationale might arise for a possible treatment with exogenous CoQ10 in dyspermic patients.
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Glutathione therapy was used for 2 months in a placebo-controlled double-blind cross-over trial of 20 infertile patients with dyspermia associated with unilateral varicocele (VAR) or germ-free genital tract inflammation (INF). The patients received either glutathione (group 1) or placebo (group 2) for 2 months, then they crossed over to the alternative treatment for a further 2 months. The patients were randomly and blindly assigned to treatment (one i.m. injection every other day of either 600 mg glutathione or an equal volume of a placebo preparation). The standard semen analysis and the computer-assisted sperm motility analyses were carried out before treatment and during the trial. Statistical cross-over analysis, case-control study and treatment efficacy test were carried out on groups 1 and 2 and differences in the effects of therapy between VAR and INF patients with varicocele or inflammation were tested. Glutathione therapy demonstrated a statistically significant positive effect on sperm motility, in particular on the percentage of forward motility, the kinetic parameters of the computerized analysis and on sperm morphology. The findings of this study indicate that glutathione therapy could represent a possible therapeutical tool for both of the selected andrological pathologies.
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On the basis of reported experimental and clinical studies we investigated the effectiveness of L-carnitine administration in a group of patients with idiopathic asthenospermia. A favourable effect of the compound on sperm motility and rapid linear progression has been shown in 37 out of 47 patients treated. In addition, the total number of sperms increased. L-carnitine was supplemented orally by a daily dosage of 3 g for three months.
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Asthenospermia is the main factor of male infertility among patients consulting the Asir Infertility Center in Abha, Saudi Arabia. Lipid peroxidation occurring in both the seminal plasma and spermatozoa was estimated by malondialdehyde (MDA) concentration. Spermatozoal MDA concentration was higher in men with decreased sperm motility. The MDA concentration in the seminal plasma exhibited no relationship with sperm concentration, sperm motility, the number of immotile spermatozoa, or even the absence of spermatozoa. The MDA concentration in sperm pellet suspensions of asthenospermic and oligoasthenospermic patients was almost twice that of the normospermic males. The MDA concentration in the sperm pellet suspension from normospermic or oligospermic patients was about 10% that in the seminal plasma. However, the MDA concentration in the sperm pellet suspension of asthenospermic or oligoasthenospermic patients was about 15% that in the seminal plasma. Treatment of asthenospermic patients with oral Vitamin E significantly decreased the MDA concentration in spermatozoa and improved sperm motility. Eleven out of the 52 treated patients (21%) impregnated their spouses; nine of the spouses successfully ended with normal term deliveries, whereas the other two aborted in the first trimester. No pregnancies were reported in the spouses of the placebo-treated patients.
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The lipid compositions and associated antioxidant capacities of spermatozoa and seminal plasma from bulls were examined at the beginning, middle and end of their reproductive period. The reduction in concentration and motility of spermatozoa associated with ageing was accompanied by a large decrease in lipid concentrations within the seminal plasma; this change in lipid concentration was accompanied by an increase in the proportion of phospholipid. By contrast, the proportion of phospholipids in the spermatozoa was significantly reduced. The major phospholipid fractions within both the spermatozoa and seminal plasma were phosphatidyl choline and phosphatidyl ethanolamine. With increasing age there was a large decrease in the proportion of phosphatidyl ethanolamine and a commensurate increase in that of phosphatidyl choline within the spermatozoa and seminal plasma. These major changes in phospholipids were accompanied by a decrease in the amount of phosphatidyl inositol and an increase in that of cardiolipin in both spermatozoa and seminal plasma. The reductions in the proportions of phosphatidyl ethanolamine were accompanied by extensive reductions in the content of the major polyunsaturated fatty acids, arachidonic 20:4 (n-6) and docosahexaenoic 22:6 (n-3); there was a decrease also in the concentration of 22:6 (n-3) in phosphatidyl choline. The changes in lipid composition owing to ageing were associated with a marked reduction within the seminal plasma of the major antioxidant enzyme systems, glutathione peroxidase and superoxide dismutase.
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Hypertrophic cardiomyopathy (HCM) is manifested by severe thickening of the left ventricle with significant diastolic dysfunction. Previous observations on the improvement in diastolic function and left ventricular wall thickness through the therapeutic administration of coenzyme Q10 (CoQ10) in patients with hypertensive heart disease prompted the investigation of its utility in HCM. Seven patients with HCM, six non-obstructive and one obstructive, were treated with an average of 200 mg/day of CoQ10 with mean treatment whole blood CoQ10 level of 2.9 micrograms/ml. Echocardiograms were obtained in all seven patients at baseline and again 3 or more months post-treatment. All patients noted improvement in symptoms of fatigue and dyspnea with no side effects noted. The mean interventricular septal thickness improved significantly from 1.51 +/- 0.17 cm to 1.14 +/- 0.13 cm, a 24% reduction (P < 0.002). The mean posterior wall thickness improved significantly from 1.37 +/- 0.13 cm to 1.01 +/- 0.15 cm, a 26% reduction (P < 0.005). Mitral valve inflow slope by pulsed wave Doppler (EF slope) showed a non-significant trend towards improvement, 1.55 +/- 0.49 m/sec2 to 2.58 +/- 1.18 m/sec2 (P < 0.08). The one patient with subaortic obstruction showed an improvement in resting pressure gradient after CoQ10 treatment (70 mmHg to 30 mmHg).
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Lipid hydroperoxides (LOOH) are the primary products of lipid peroxidation. Therefore, it would be desirable to detect and identify the lipid hydroperoxides in tissues or blood. One of the most advanced methods for the detection of LOOH is a chemiluminescence-based high-performance liquid chromatography (HPLC) assay (1–5) as shown in Fig. 1. The reaction sequence leading to the emission of light from isoluminol in the presence of LOOH and microperoxidase, a heme catalyst, is assumed to be as follows:
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Total radical-trapping antioxidant potential (TRAP) measurements of human seminal plasma (N = 25) were performed by using a post-addition assay based on trapping 2,2' Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radicals. This method enables the antioxidant capacity of human seminal plasma and its constituents to be quantified. The standard procedure consisted of determination of the Trolox equivalent antioxidant capacity (TEAC) after incubating the test sample in the ABTS radical solution for 10 seconds (fast TRAP) and 300 s (total TRAP). Interestingly, seminal plasma showed a fast TRAP and a high slow TRAP (Total TRAP - Fast TRAP). The final total TRAP of seminal plasma is about 10 times higher than that of blood plasma. Various components of seminal plasma contribute to its fast TRAP; 37% can be attributed to vitamin C, uric acid, and tyrosine; proteins and polyphenolic compounds contribute a further 57%. In contrast, the slow TRAP was attributed to vitamin C (1%), uric acid (2%), and tyrosine (15%) and to proteins and polyphenolic compounds (33%). It was not possible to account for the remaining 49%. Neither known putative antioxidants, such as spermine, pyruvate, and taurine, nor other seminal compounds, such as carnitine, sialic acid, fructose, spermidine, glycerophosphorylcholine, and hyaluronic acid, contributed to any significant radical-trapping activity at a standard concentration of 1 mM. Of the amino acids, only tyrosine possessed a slow TRAP, and it is present at a high concentration in seminal plasma. Glutathione and hypotaurine show high fast and slow TRAPs, respectively. However, because of their low concentration in seminal plasma, their contribution to the TRAP is negligible. In conclusion, seminal plasma possesses a high antioxidant buffer capacity that protects spermatozoa from oxidative stress. Moreover, these findings suggest that the fast and slow TRAPs may have an important role as infertility markers and treatment targets in future antioxidant therapies.
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We have recently shown that patients with prostato-vesiculo-epididymitis (PVE) have a greater reactive oxygen species (ROS) overproduction than patients with prostatitis or prostato-vesiculitis. Since this biochemical stress persists even after treatment with antimicrobials, it may relate to an imbalance between pro- and anti-oxidant factors at the epididymal level. To evaluate the effects of antioxidant treatment of patients with PVE, whether in the presence or absence of pro-oxidant factors, abacterial PVE infertile patients with normal (<1x10(6)/ml, group A, n = 34) or abnormal (>1x10(6)/ml, group B, n = 20) seminal white blood cell (WBC) concentrations received carnitines (L-carnitine 1 g and acetyl-carnitine 0.5 g twice/day) for 3 months followed by a wash-out period of 3 months. Semen parameters, ROS production and pregnancy outcome were evaluated before, during and following carnitine treatment. Carnitines increased sperm forward motility and viability in group A patients. This was associated with a significant reduction in ROS production which persisted during wash-out. Carnitines increased only the percentage of viable spermatozoa in group B patients. Within 3 months after the discontinuation of carnitines, the rate of spontaneous pregnancy in group A patients was significantly higher than that of group B patients, being 11.7% (4/34) compared with 0%. These results indicate that carnitines are only an effective treatment in patients with abacterial PVE and elevated ROS production when seminal WBC concentration is normal.
Article
Levels of coenzyme Q10 (CoQ10) and of its reduced and oxidized forms (ubiquinol, QH2, and ubiquinone, Qox) have been determined in sperm cells and seminal plasma of idiopathic (IDA) and varicocele-associated (VARA) asthenozoospermic patients and of controls. The results have shown significantly lower levels of coenzyme Q10 and of its reduced form, QH2, in semen samples from patients with asthenospermia; furthermore, the coenzyme Q10 content was mainly associated with spermatozoa. Interestingly, sperm cells from IDA patients exhibited significantly lower levels of CoQ10 and QH2 when compared to VARA ones. The QH2/Qox ratio was significantly lower in sperm cells from IDA patients and in seminal plasma from IDA and VARA patients when compared with the control group. The present data suggest that the QH2/Qox ratio may be an index of oxidative stress and its reduction, a risk factor for semen quality. Therefore, the present data could suggest that sperm cells, characterized by low motility and abnormal morphology, have low levels of coenzyme Q10. As a consequence, they could be less capable in dealing with oxidative stress which could lead to a reduced QH2/Qox ratio. Furthermore, the significantly lower levels of CoQ10 and QH2 levels in sperm cells from IDA patients, when compared to VARA ones, enable us to hypothesize a pathogenetic role of antioxidant impairment, at least as a cofactor, in idiopathic forms of asthenozoospermia.
Article
The objective of this work was to evaluate the capability of both seminal plasma and sperm cells to scavenge different forms of oxyradicals and the possible correlation with sperm motility parameters. A total of 14 individuals were analyzed by computer-assisted sperm analysis (CASA) and the results integrated with the measurement of total oxyradical scavenging capacity (TOSC) toward peroxyl radicals, hydroxyl radicals and peroxynitrite in seminal plasma and spermatozoa. TOSC values revealed some significant correlation with kinetic sperm cell parameters, including curvilinear velocity (VCL), straight-line velocity (VSL) and linearity (LIN). A lower antioxidant capacity toward hydroxyl radical was found in the seminal fluid of men with reduced sperm motility. Such correlations were not found with peroxyl radicals and peroxynitrite, neither when TOSC values were analyzed in spermatozoa. The TOSC assay is a useful tool for studying the relationship between oxyradical toxicity and abnormal sperm cell motility. Although further investigations are needed, the data clearly establish different role for various forms of oxyradicals, i.e., hydroxyl radicals, in altering sperm motility. Measurement of TOSC is suggested as a useful means of indicating relationship between reactive oxygen species and sperm cell kinetics in clinical trials and antioxidant-based treatments.