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The protective role of ubiquinol-10 against formation of lipid hydroperoxides in human seminal fluid

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The protective role of ubiquinol-10 against formation of lipid hydroperoxides in human seminal fluid

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Abstract

Defective sperm function in infertile men has been associated with increased lipid peroxidation and impaired function of antioxidant defenses in spermatozoa. Evidence strongly suggests that CoQ10, a lipid-soluble component of the respiratory chain acts, in its reduced form (ubiquinol), as a potent antioxidant in various biological systems, such as lipoproteins and membranes. In this study we assayed CoQ10 content in both the reduced and oxidized form (ubiquinol/ubiquinone), and hydroperoxide levels in seminal plasma and seminal fluid from 32 subjects with a history of infertility. Our results showed a significant correlation between ubiquinol content and sperm count (r = 0.62; P < 0.05) in seminal plasma. An inverse correlation between ubiquinol content and hydroperoxide levels both in seminal plasma and in seminal fluid (r = -0.56; P = 0.01) was found. Using multiple regression analysis we also found a strong correlation among sperm count, motility and ubiquinol-10 content (P < 0.01) in seminal fluid. An inverse correlation between ubiquinol/ubiquinone ratio and percentage of abnormal morphology was also observed in total fluid. These results suggest that ubiquinol-10 inhibits hydroperoxide formation in seminal fluid and in seminal plasma. Since peroxidation in sperm cells is an important factor affecting male infertility, ubiquinol could assume a diagnostic and/or a therapeutic role in these patients.

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... CoQ10 is detectable in human seminal fluid and shows direct correlation with seminal parameters [23]. Its antioxidant properties are directly related to sperm protection, as suggested by the inverse correlation between hydroperoxides and ubiquinol (CoQ10 reduced fraction) in seminal fluid [24]. Furthermore, CoQ10's role as anti-inflammatory molecule has been recently evaluated. ...
... A total of 65 patients were selected. Varicocele diagnosis was clinical and confirmed by Doppler technique [24]. After 3-5 days of sexual abstinence, semen samples were collected and placed at 37 • C for liquefaction. ...
... C. Idiopathic oligo-, asteno-, oligoastenozoospermia (IDIO), 24 patients, median age and interquartile range 37 (33.5-40.5) years, BMI 24 (20)(21)(22)(23)(24)(25)(26)(27) kg/m 2 , 30% smokers. We used the term "idiopathic" referring to seminal abnormalities of unknown etiologies, according to literature indication [51][52][53][54]. ...
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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.
... Furthermore, higher seminal fluid concentrations of CoQ10 are correlated with higher sperm concentrations and motility. 7 Whether these improvements in semen parameters translate to higher rates of conception is unclear. A recent meta-analysis including 3 randomized controlled trials revealed that CoQ10 supplementation increases CoQ10 concentration in seminal fluid and improves sperm concentration and motility. ...
... 24 Even using the reduced form of CoQ10, ubiquinol, Safarinejad et al reported improvements in sperm concentration, motility, and morphology of 228 infertile men with idiopathic oligoasthenoteratospermia. 25 Furthermore, higher seminal fluid concentrations of CoQ10 are correlated with higher sperm concentrations and motility. 7 CoQ10 serum and semen concentrations are linearly correlated such that CoQ10 supplementation of 30 mg and 100 mg daily resulted in a 1.47-and 2.16-fold increase in plasma concentrations, respectively. 26 The linear correlation between the amount of CoQ10 supplementation and serum concentrations has been shown to be sustained until a dose of 2400 mg/day, at which point a plateau in plasma concentration is achieved. ...
Article
Objective: To assess the association between coenzyme Q10 (CoQ10) intake from food sources and semen quality. We assessed this association in a prospective cohort of men attending a fertility clinic. CoQ10 supplementation has been associated with improvements in semen parameters. However, impact of CoQ10 intake from food sources on semen quality has not been investigated. Methods: Subfertile couples seeking fertility evaluation at the Massachusetts General Hospital Fertility Center were invited to participate in an ongoing study of environmental factors and fertility. In total, 211 male participants completed a validated food frequency questionnaire and provided 476 semen samples. Multivariable linear mixed models were used to examine the relation between CoQ10 intake from foods and semen parameters while adjusting for potential confounders and accounting for within-person correlations. Results: Mean dietary CoQ10 intake was 19.2 mg/day (2.4-247.2 mg/day). No subjects were taking CoQ10 supplements. There were no associations between dietary CoQ10 intake from foods and conventional semen parameters. The adjusted mean difference (95% confidence interval) comparing men in the top and bottom quartiles of CoQ10 intake from foods were -3.1 mil/mL (95% CI -29.5, 38.8 mil/mL) for sperm concentration, -4.5% (-15.1%, 6.0%) for total motility, -1.3% for progressive motility (-8.4%, 5.7%) and 0.3% (-1.4%, 2.0%) for sperm morphology. Conclusions: CoQ10 intake from foods was not related to semen parameters among subfertile men. Mean dietary intake of CoQ10 in this study was 10-fold lower than the supplemental dose used in clinical trials showing improved sperm motility. CoQ10 intake from foods alone may be insufficient to optimize semen parameters.
... Ubiquinol is a strong lipophilic antioxidant; it can regenerate other antioxidants such as vitamin E and vitamin C. The ubiquinol concentration in the body is approximately 90% of the total CoQ 10 . A strong correlation has been reported to exist between sperm count, motility, and ubiquinol concentration in seminal fluid [8]. CoQ 10 biosynthesis is very active in the testes and high levels of ubiquinol are present in sperm [9,10]. ...
... Ubiquinol (CoQ 10-RED ) is a stronger antioxidant in comparison with ubiquinone. A significant correlation between ubiquinol content and sperm count and motility in seminal fluid of infertile men was reported [8]. When infertile men were treated with 150 mg ubiquinol daily during four months, total sperm count was increased by 53% and sperm motility by 26% and sperm morphology was also improved [32]. ...
Article
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Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme , γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, , and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.
... So, process of ATP synthesis and energy generation is related to the availability and existence of CoQ 10 in the sperm cell [12]. A study reported a strong correlation between motility and CoQH 2 content in seminal fluid [13]. A significant increase in sperm motility has been led by administration of CoQ 10 in infertile men with idiopathic asthenozoospermia [14]. ...
... There is little published information on the influence of CoQ 10 on sperm quality. Exogenous administration of CoQ 10 was effective in improving sperm quality, M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT especially motility in infertile men [13,222324. This is in agreement with results of the present study. ...
Article
The purpose of this study was to determine the effects of different concentrations of coenzyme Q10 (CoQ10) and α-tocopherol (T) along with their interaction effects on the quality of preserved stallion semen at 5C for a period of 48 h. Semen was collected and diluted with skim milk-based extender that was supplemented with different antioxidants: no antioxidant (negative control, NC), 0.9% (v/v) dimethyl sulfoxide (positive control, PC), α-tocopherol [5 (T5) or 10 (T10) Mm], CoQ10 [1 (C1) or 2 (C2) μM], 1μM CoQ10 + 5mM α-tocopherol (C1T5), 1μM CoQ10 + 10mM α-tocopherol (C1T10), 2μM CoQ10 + 5mM α-tocopherol (C2T5) and 2μM CoQ10 + 10mM α-tocopherol (C2T10), then kept at 5ᵒC. The results showed that C1 extender resulted in higher total motility (62.44±3.82) and plasma membrane integrity (65.16±3.63%) compared to negative control after 48 h of storage (P < 0.05). Different concentrations of α-tocopherol had no significant effects on sperm quality, with the exception of plasma membrane integrity, compared to NC and PC extender (P > 0.05). Also, C1T5 extender improved total and progressive motility, plasma membrane integrity and functionality, and decreased lipid peroxidation compared to NC and C2T10 extenders over 48 h of storage at 5ᵒC (P < 0.05). The C1T5 extender was similar to C1 and T5 extenders in all semen parameters evaluated during storage time. In conclusion, between above-mentioned extenders, C1T5 could improve stallion sperm quality during 48 h of storage. In the present study, none of extenders had effect on sperm quality until 24 h storage.
... A strong correlation among sperm count, motility and ubiquinol-10 content in seminal fluid has been reported. 9 In a recent study exogenous administration of CoQ10 was effective for improving sperm kinetic features in patients with idiopathic asthenozoospermia. 10 To our knowledge, while a previous RCT exists of the role of CoQ10 supplementation in semen parameters, this is the first study to look at sperm function and the hormone profile in infertile men with idiopathic oligoasthenoteratospermia. ...
... Conversely, Littarru and Tiano [29] observed that supplementation with CoQ10 resulted in increased levels of ubiquinol-10 within the circulating lipoproteins and increased resistance of human low-density lipoproteins to the initiation of lipid peroxidation, which could reduce oxidative stress. Alleva et al. [4] measured the content of both the reduced and oxidised forms of CoQ10 (ubiquinol/ubiquinone) as well as the organic peroxide concentrations in seminal plasma and seminal fluid in 32 infertile patients. A significant positive correlation was observed between ubiquinol content, motility and sperm count; an inverse correlation between ubiquinol content and organic peroxide concentrations was also observed . ...
Article
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To evaluate the effect of coenzyme Q10 treatments in male infertility, specifically in these parameters: live birth and pregnancy rates, CoQ10 seminal concentration, sperm concentration, and sperm motility. Systematic review and meta-analysis in male infertility patients with CoQ10 oral treatments. Three trials were included: 149 males in CoQ10 group and 147 males in placebo group. None of the included trials provided any data regarding live births. The results of this meta-analysis show that supplementing infertile men with CoQ10 does not increase pregnancy rates. The analysis showed, among patients receiving CoQ10 treatment, a statistically significant increase in: CoQ10 seminal concentration (RR 49.55, 95 % CI 46.44 to 52.66, I(2) = 17 %), sperm concentration (RR 5.33, 95 % CI 4.18 to 6.47, I(2) = 58 %), and sperm motility (RR 4.50, 95 % CI 3.92 to 5.08, I(2) = 0 %) CONCLUSION: There is no evidence in the literature that CoQ10 increases either live birth or pregnancy rates, but there is a global improvement in sperm parameters. Adequately powered, robust trials of individual and combination antioxidant therapies are required to guide clinical practice.
... Evidence suggests that lycopene, which is found in abundance in tomatoes, can be ten times more potent that vitamin E in binding singlet oxygen and protecting the plasma membrane (Di Mascio et al. 1989). Coenzyme Q10 is found in the sperm mid-piece (Lewin and Lavon 1997) and has been demonstrated to inhibit H 2 O 2 formation in both seminal fluid and seminal plasma (Alleva et al. 1997). In contrast, carnitines are dietary antioxidants that improve sperm motility and remove excess intracellular toxic acetyl-CoA, which is a substrate for mitochondrial ROS production . ...
Chapter
Many studies have implicated the role of reactive oxygen species in male infertility. While reactive oxygen species has a physiological role in maintenance and function of the spermatozoa, excessive levels above the sperm defense leads to detrimental effects on sperm function and integrity. These possible detrimental effects are termed oxidative stress. Ever since leukocytes were discovered in semen, it has been suggested as a source for the reactive oxygen species found in semen samples. Evidence indicates that leukocytospermia, which is an abnormally high amount of leukocytes in the semen (>1.0 × 10 6 leukocytes/ml of semen), is associated with poor semen parameters. Leukocytospermia can be symptomatic when it is a result of a urinary tract infection, such as prostatitis, but it can also be asymptomatic. With multiple etiologies, from bacterial causes to idiopathic causes, the methods of treatment for leukocytospermia include antioxidant and antibiotic supplementation. The success of these treatments, however, is greatly debated. Nonetheless, understanding the role of leukocytospermia in male factor infertility is essential because of the increasing evidence that oxidative stress does produce detrimental effects on sperm quality.
... CoQ10 recycles vitamin E and prevents its pro-oxidant activity (18). QH2 also acts as an antioxidant by preventing lipid peroxidation, whereas CoQ10 inhibits hydrogen peroxide formation in the seminal fluid and seminal plasma of infertile men (19). ...
Article
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Objective: Overproduction of reactive oxygen species results in oxidative stress, a deleterious process that damages cell structure as well as lipids, proteins, and DNA. Oxidative stress plays a major role in various human diseases, such as oligoasthenozoospermia syndrome. Materials and methods: We evaluated the effectiveness of antioxidant co-supplementation therapy using vitamin C, vitamin E, and coenzyme Q10 in men with oligoasthenozoospermia. Overall, 169 infertile men with oligoasthenozoospermia received antioxidant therapy with 80 mg/day vitamin C, 40 mg/day vitamin E, and 120 mg/day coenzyme Q10. We evaluated spermiogram parameters at baseline and at 3 and 6 months of follow-up. Results: Significant improvements were evident in sperm concentration and motility following coenzyme Q10 therapy. Treatment resulted in 48 (28.4%) partner pregnancies, of which 16 (9.5%) were spontaneous. Significant improvements in sperm cell concentration and sperm motility were observed after 3 and 6 months of treatment. Conclusions: Vitamin C, vitamin E, and coenzyme Q10 supplementation resulted in a significant improvement in certain semen parameters. However, further studies are needed to empirically determine the effect of supplementation on pregnancy rate.
... It is noteworthy that the only lipid-soluble antioxidant producing in our body is Co-Q10, preventing oxidation of proteins, fats and DNA (Ernster, 1993). Co-Q10 is effective on sperm quality and motility, especially in infertile men (Mancini et al. 1998;Alleva et al. 1997;Lee et al. 2006) which are in accordance with the results of our study, due to the improvement of sperm motility. Generally, the better effect of Co-Q10 on sperm motility in comparison ellagic acid may be due to the bioenergetics role of Co-Q10 in the respiratory chain and the production of ATP (Turunen et al. 2004;Almeida and Ball, 2005). ...
Article
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The aim of this study was to determine the effects of co-Q10 and ellagic acid on sperm parameters after the freeze-thawing of Ghezel ram sperm. Twenty ejaculates from five Ghezel rams were collected in this study. Semen samples, which were diluted with a soybean lecithin (SL) based extender containing 0.25 mM ellagic acid, 0.5 μM co-Q10, 0.25 mM ellagic acid + 0.5 μM co-Q10 and no antioxidant (control), were cooled to 4°C, frozen in 0.25 mL French straws and stored in liquid nitrogen. Sperm motility characteristics, membrane integrity, abnormal morphology, lipid peroxidation and antioxidant activities (glutathione peroxidase, superoxide dismutase and total antioxidant capacity) were evaluated following freeze-thawing. The results showed that 0.5 μM Co-Q10, improved viability, total motility parameters and decreased abnormal sperm and improved linearity (LIN), curvilinear velocity (VCL), straight-line velocity (VSL) and path velocity (VAP) parameters (P < 0.05). Ellagic acid and the treatment with a combination (0.25 mM ellagic acid+0.5 μM co-Q10) improved viability and total motility parameters (P < 0.05). The additives did not affect the maintenance of superoxide dismutase (SOD) and glutathione peroxidase (GPx), when compared to the control. It can be concluded that addition of 0.5 μM co-Q10 improved the post-thawing quality of ram semen.
... The antioxidant property of CoQ10 serves to protect the vital organ heart from circulating low-density lipoprotein. Therapeutically, CoQ10 proved to be useful in cardiovascular disorders, i.e., congestive heart failure, cardiomyopathy, angina pectoris, hypertension, myocardial infarction [5], Parkinson disease [6], diabetes mellitus [7], asthenozoospermia (make infertility or low sperm motility) [8], cancer [9], and periodontal disease [10]. Several work reported for improving bioavailability such as solid dispersion of CoQ10 with tyloxapol [11], formulation with different solubilizing agent, hydrogenated lecithin [12], and complexes with beta cyclodextrin [13]. ...
Article
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Purpose Coenzyme (CoQ10) is a poorly soluble drug strategically selected to enrich oral bioavailability by incorporating in solid self-nanoemulsifying drug delivery system (s-SNEDDS) comprised of oil, surfactant, and cosurfactant. The conventional self-emulsifying drug delivery system (SEDDS) and liquid SNEDDS (l-SNEDDS) usually have the problem of drug instability and precipitation. Methods The selected oils, surfactant, and cosurfactant with maximum drug solubility were Lauroglycol FCC, Labrasol, and Transcutol P. The ternary phase diagrams were constructed, and selected formulations from ternary phase diagrams were subjected to thermodynamic stability and self-dispersibility test and characterized for emulsion droplet size and droplet size distribution. The optimized formulation was comprised of Lauroglycol FCC 20 % (w/w), Labrasol 10 % (w/w), and Transcutol P 20 % (w/w) as oil, surfactant, and cosurfactant. Results The transmission electron microscopy (TEM) study of optimized l-SNEDDS reported mean globule size of 34 nm was transformed into s-SNEDDS by spray-drying technique using solid carrier. The s-SNEDDS was characterized for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and X-ray diffraction (X RD). The in vitro release profile of s-SNEDDS showed drug release (97.5 ± 4.5 %), marketed formulation (57.96 ± 0.54 %), and CoQ10 powder (0.36 ± 0.06 %) in 1 hour. The pharmacokinetic study of optimized s-SNEDDS in male Wistar rats revealed the improved maximum concentration (C max) (3.4-fold vs CoQ10 powder; 1.4-fold vs marketed formulation) and area under the curve (AUC) (5-fold vs CoQ10 powder; 2-fold vs marketed formulation). With this result, s-SNEDDS could be of potential to enhance the oral bioavailability of CoQ10. Conclusion Thus, s-SNEDDS in addition to enhancing the dissolution and oral bioavailability often results in low production cost, easy processing, and better patient compliance.
... 9 Decreased serum CoQ 10 concentrations as well as a decrease in the CoQ 10 H 2 -to-ubiquinone ratio have been demonstrated in diseases associated with OS. 10 A strong correlation among sperm count, motility and ubiquinol-10 levels in seminal fluid has also been reported. 11 In this study, the first on this subject to our knowledge, we determined the effects of the exogenous administration of ubiquinol in the improvement of semen parameters. ...
Article
We investigated the effects of the administration of ubiquinol (a reduced form of coenzyme Q(10)) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia. A total of 228 men with unexplained infertility were randomly assigned 1:1 into 2 groups. Group 1 (114) received 200 mg ubiquinol daily by mouth for 26 weeks and group 2 (114) received a similar regimen of placebo. After completion of the 26-week treatment phase, all participants were followed for another 12-week off-drug period. Primary outcomes were improvement in sperm density, sperm motility and sperm strict morphology. At the end of the 26-week treatment period mean ± SD sperm density in the ubiquinol and placebo groups was 28.7 ± 4.6 × 10(6)/ml and 16.8 ± 4.4 × 10(6)/ml (p = 0.005), sperm motility was 35.8% ± 2.7% and 25.4% ± 2.1% (p = 0.008), and sperm strict morphology was 17.6% ± 4.4% and 14.8% ± 4.1% (p = 0.01) of normal sperm, respectively. During the treatment period serum follicle-stimulating hormone levels decreased significantly (p = 0.02) and serum inhibin B concentrations increased significantly (p = 0.01). During the off-drug period semen parameters gradually returned to baseline values but the differences were still significant for sperm density (p = 0.03) and sperm motility (p = 0.03). The correlation coefficients analysis revealed a positive association between the duration of treatment with ubiquinol and sperm density (r = 0.74, p = 0.017), sperm motility (r = 0.66, p = 0.024) and sperm morphology (r = 0.57, p = 0.027). Ubiquinol was significantly effective in men with unexplained oligoasthenoteratozoospermia for improving sperm density, sperm motility and sperm morphology.
... In men, the amount of CoQ10 in the seminal fluid shows a direct correlation with semen parameters. A strong correlation between sperm count, motility and ubiquinol (reduced from of CoQ10) has been reported [66,67]. Reduced levels of CoQ10 were noted in infertile men with idiopathic and varicocele-associated asthenospermia [68]. ...
Article
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Background Infertility is a relatively common condition. When patients are confronted with this diagnosis, there are medical, psychological, and financial sequelae. Patients often wonder if there is anything they can do to optimize their natural fertility or increase the effectiveness of infertility treatments. Findings If there is a clear impact on fertility, such as with smoking and alcohol, cessation should be advised. Similarly, weight loss should be recommended if the BMI is in the overweight and obese category, and weight gain should be recommended for an underweight BMI. The evidence surrounding other lifestyle modifications is less clear. There are conflicting data regarding an optimal fertility diet and consumption of vitamins and supplements. Antioxidants seem to improve semen parameters in men, but the effect on female fertility is less clear. If conflicting evidence exists, such as with caffeine consumption or exercise, moderation should be emphasized. Finally, the diagnosis of infertility and subsequent fertility treatments are stressful for both partners. The psychological aspects should not be ignored and methods such as yoga and cognitive behavioral therapy may be beneficial. Conclusion Continued research will determine the optimal lifestyle modifications to achieve pregnancy.
... It was also verified whether the addition of nonenzymatic antioxidants, associated or not, was effective in reducing LPO levels of cooled semen. The ubiquinol, reduced form of the CoQ10, acts as a potent antioxidant in several biological systems such as lipoproteins and membranes, protecting them from oxidation and avoiding the formation of hydroperoxides, thus preventing the LPO (Alleva et al. 1997;Bentinger et al. 2007;Carocho and Ferreira 2013). Another important function of CoQ10 is the regeneration of a-TOH from the radical a-TOH (Crane and Navas 1997). ...
Article
Full-text available
Biotechnology applied for equine semen increases the levels of reactive oxygen species and reduces the natural antioxidant defence, by both dilution and removal of seminal plasma. Therefore, the aims of this study were to evaluate the effect of adding coenzyme Q10 (CoQ10) and α-tocopherol (α-TOH) to the cooling extender, singly or in combination, on sperm parameters, and their effectiveness in preventing lipid peroxidation (LPO) of equine semen during cooling at 5°C for 72 h. Ten adult stallions of proven fertility were used, using two ejaculates each, subjecting them to the treatments with the following concentrations: α-TOH: 2 mm; CoQ10: 40 μg/ml; and CoQ10 + α-TOH: 40 μg/ml + 2 mm for control (C) without the addition of antioxidants and for vehicle control (EtOH) with 100 μl ethanol. The CoQ10 group had a higher percentage of total motility (69.1 ± 16.2%) compared to control (62.1 ± 16.2%) and EtOH (58.1 ± 18.6%). CoQ10 + α-TOH and α-TOH groups were most effective in preventing LPO compared to controls (1765.9 ± 695.9, 1890.8 ± 749.5, 2506.2 ± 769.4 ng malondialdehyde/10(8) sptz, respectively). In conclusion, CoQ10 and α-TOH were effective during the cooling process of equine semen at 5°C for 72 h, providing increased levels of total motility, as well as lower LPO.
... This has directed studies towards investigating the role of CoQ as an antioxidant under in vivo conditions. Major studies on the role of this molecule includes 1) monitoring the level of the molecule in the different tissues following supplementation with different diet regimes in different animal models [21 -26]; 2) the attenuation of the oxidative post-translational modifications [21,27]; 3) reversal of the age-related deterioration of cognitive ability or learning ability [27,28]; 4) alterations in level of mitochondrial α-tocopherol by the molecule [12]; 5) modulation of lipid peroxidation in diabetic models [29]; 6) reduction in H 2 O 2 -mediated DNA damage in human lymphocytes [30]; 7) alterations in gene expression [31,32]; 8) correlation with male infertility [33] and its role in sperm motility [34]; 9) life span [24, 35 -37], etc. ...
Article
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Background Two series of 4-benzylidene-6-(4-methyl-phenyl)-4,5-dihydropyridazin-(2H)-one compounds (3a-e) and 4-benzylidene-6-(4-chloro-phenyl)-4,5-dihydropyridazin-(2H)-ones (3f-j) were synthesized and evaluated as anticonvulsant agents. Methods Synthesized compounds (3a-3j) were tested against maximum electro shock (MES) and Isoniazid (INH) induced convulsion methods for anticonvulsant activities and neurotoxicity. Results In MES induced convulsions, result found that the compounds 3e and 3j exhibited highest anticonvulsant activities. In INH induced convulsions, result was indicated that all the compounds exhibited good anticonvulsant activities., whereas compounds 3d and 3j showed maximum activity. Methyl derivatives were more active than chloro derivatives. Phenytoin sodium (25mg/kg) and sodium vaproate (50mg/kg) were used as reference drugs. All these synthesized pyridazinone compounds (3a-j) did not exhibit any neurotoxicity up to 100 mg/kg dose levels. Conclusion All compounds showed good anticonvulsant activities against both MES and INH induced convulsion models. Many such explorations are anticipated in the near future.
... Alleva et al. reported a significant negative correlation between Co-Q10 levels and H O . [54] Several studies have assessed the impact of CoQ-10 on semen parameters in patients with iOAT. Safarinejad randomly assigned 212 infertile men with iOAT to receive 300 mg Co-Q10 orally or placebo for a period 26 weeks. ...
Article
Oxidative stress, the state of imbalance between re- active oxygen species (ROS) and antioxidants, is an established cause of male infertility. In light of the ex- traordinary high content of polyunsaturated fatty acids in the sperm plasma membrane as well as a lack of relevant defense mechanisms, sperm cells are par- ticularly vulnerable to the damaging effects of ROS, which are capable of eliciting sperm DNA damage and accelerating apoptosis. In the past few decades, interest in antioxidant supplementation had emerged in an attempt to restore the equilibrium between oxi- dation and antioxidant protection. While many com- pounds have been investigated, the search for the optimal antioxidant regimen continues. The purpose of this review is to explore the available literature on antioxidant therapy in infertile men, evaluating its ef- cacy both in vivo and in vitro on different semen pa- rameters and pregnancy outcomes.
... Alleva et al. reported a significant negative correlation between Co-Q10 levels and H 2 O 2 . [54] Several studies have assessed the impact of CoQ-10 on semen parameters in patients with iOAT. Safarinejad randomly assigned 212 infertile men with iOAT to receive 300 mg Co-Q10 orally or placebo for a period 26 weeks. ...
Article
Introduction: Idiopathic oligoasthenoteratozoospermia (iOAT) is commonly encountered during the evaluation of men with infertility. Antioxidants have been utilized empirically in the treatment of iOAT based on their ability to reverse oxidative stress (OS)-induced sperm dysfunction often encountered in this patient population. Methods: A literature search was performed using MEDLINE/PubMed, focusing on publications of antioxidant therapies for iOAT. The main objective of our review article was to report the rationale and available evidence supporting the use of antioxidants. Results: Antioxidants such as glutathione, vitamins E and C, carnitines, coenzyme-Q10, N-acetylcysteine, selenium, zinc, folic acid, and lycopene have been shown to reduce OS-induced sperm damage. While rigorous scientific evidence in the form of double-blind, placebo-controlled clinical trials is limited, recent systematic reviews and meta-analyses have reported a beneficial effect of antioxidants on semen parameters and live birth rates. Conclusion: Additional randomized controlled studies are required to confirm the efficacy and safety of antioxidant supplementation in the medical treatment of idiopathic male infertility as well as the dosage required to improve semen parameters, fertilization rates, and pregnancy outcomes in iOAT.
... It is noteworthy that the only lipid-soluble antioxidant producing in our body is Co-Q10, preventing oxidation of proteins, fats and DNA (Ernster, 1993). Co-Q10 is effective on sperm quality and motility, especially in infertile men (Mancini et al. 1998;Alleva et al. 1997;Lee et al. 2006) which are in accordance with the results of our study, due to the improvement of sperm motility. Generally, the better effect of Co-Q10 on sperm motility in comparison ellagic acid may be due to the bioenergetics role of Co-Q10 in the respiratory chain and the production of ATP (Turunen et al. 2004;Almeida and Ball, 2005). ...
... Oral supplementation with 60 mg of CoQ- 10 in these infertile men was seen to improve fertilisation rate without effecting semen parameters (Thomas et al., 1997). Oral CoQ-10 administration has been shown to inhibit hydrogen peroxide formation in seminal fluid (Alleva et al., 1997). Catalase is another antioxidant which should be further investigated for its ability to detoxify both intracellular and extracellular hydrogen peroxide to water and oxygen (Baker et al., 1996). ...
Article
Oxidative stress contributes to defective spermatogenesis leading to male factor infertility. The aim of this study was to review the current literature on the effects of various antioxidants to improve fertilisation and pregnancy rates. The sources of literature were Pubmed and the Cochrane data base. Reviewing the current literature revealed that Carnitines and vitamin C and E have been clearly shown to be effective by many well-conducted studies and may be considered as a first line treatment. The efficacy of antioxidants, such as glutathione, selenium and coenzyme Q10 has been demonstrated by few, but well-performed studies, and may be considered second line treatment. There is, however, a need for further investigation with randomised controlled studies to confirm the efficacy and safety of antioxidant supplementation in the medical treatment of idiopathic male infertility as well as the need to determine the ideal dose of each compound to improve semen parameters, fertilisation rates and pregnancy outcomes.
... Concerning the spermatozoa, CoQ-10 is mostly concentrated in the midpiece being used for ATP-dependent processes such as sperm motility (Lewin and Lavon, 1997). Moreover, ubiquinol (a reduced form of CoQ-10) acts as a strong antioxidant in several biological systems (such as membranes and lipoproteins) by protecting them from hydroperoxides formation and lipid peroxidation (Alleva et al., 1997;Bentinger et al., 2007). These important CoQ-10 properties suggests superior preservation (statistical tendency) of sperm membrane characteristics for the treated groups of present study, where higher mitochondrial membrane potential (HMMP) and fully intact cells (PIAIHM) were observed compared with control group (Table 2). ...
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Coenzyme Q-10 (CoQ-10) is a cofactor for mitochondrial electron transport chain and may be an alternative to improve sperm quality of cryopreserved equine semen. This work aimed to improve stallion semen quality after freezing by adding CoQ-10 to the cryopreservation protocol. Seven saddle stallions were utilized. Each animal was submitted to five semen collections and freezing procedures. For cryopreservation, each ejaculate was divided in three treatments: 1) Botucrio® diluent (control); 2) 50 μmol CoQ-10 added to Botucrio® diluent; 3) 1 mmol CoQ-10 added to Botucrio® diluent. Semen batches were analyzed for sperm motility characteristics (CASA), plasma and acrosomal membranes integrity and mitochondrial membrane potential (by fluorescence probes propidium iodide, Hoechst 33342, FITC-PSA and JC-1, respectively), alterations in cytoskeletal actin (phalloidin-FITC) and mitochondrial function (diaminobenzidine; DAB). The 1 mmol CoQ-10 treatment presented higher (P<0.05) amount (66.8%) of sperm cells with fully stained midpiece (indicating high mitochondrial activity) and higher (P<0.05) amount (81.6%) of cells without actin reorganization to the post-acrosomal region compared to control group (60.8% and 76.0%, respectively). It was concluded that the addition of 1 mmol CoQ-10 to the freezing diluent was more effective in preserving mitochondria functionality and cytoskeleton of sperm cells submitted to cryopreservation process.
... Interestingly, SERM in combination with CoQ10 significantly improved sperm quality, especially for men with OA. It has been demonstrated that CoQ10 plays an important role in both energy metabolism and lipid peroxidation in spermatozoa [100]. Supplementation of CoQ10 significantly increased not only the antioxidative capability of spermatozoa, but also sperm quality, such as motility; that is, there is a positive correlation between CoQ10 and sperm motility in infertile men [101,102]. ...
Article
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In this study, we used a network meta-analysis (NMA) to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment. Medline, Excerpta Medica Database (EMBASE), Ovid, and China National Knowledge Infrastructure (CNKI), were searched for the period from January 1990 to June 2021 using the keywords “male infertility,” “medical therapy,” “supplement/nutrient therapy,” and related terms. Studies involving randomized controlled trials (RCTs) investigating medicines (mainly follicle-stimulating hormone (FSH), androgen, and clomiphene/tamoxifen) or supplements (mainly zinc, selenium, vitamin C or E, carnitine, coenzyme Q10 (CoQ10), or combined treatment) for idiopathic infertile men were selected for meta-analysis. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) was used for data extraction, and a risk-of-bias tool and grades of recommendation, assessment, development, and evaluation (GRADE) system adapted to the NMA were employed to assess the quality of the evidence. The primary outcomes were live birth and spontaneous pregnancy rate (SPR). The secondary outcomes were sperm parameters (including concentration, progressive motility, and morphology) and side effects. In total, 65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included. A total of 36 studies reported SPR but only three reported live birth rates. The quality of the included studies was found to be moderate to high. Compared with a placebo or being untreated, carnitine plus vitamins significantly improved SPR (relative risk (RR) = 3.7, 95% confidence interval (CI), 1.6–8.5); fatty acids significantly increased sperm concentrations (mean difference (MD) = 12.5 × 10⁶ mL–1, 95%CI, 3.1 × 10⁶–22.0 × 10⁶); and selective estrogen receptor modulators (SERM) plus CoQ10 significantly improved sperm progressive motility (MD = 11.0%, 95%CI, 0.1%–21.9%) and normal sperm morphology (MD = 11.0%, 95%CI, 4.6%–17.4%). The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations, respectively, even after excluding trials at a high risk of bias. Compared with a placebo or being untreated, FSH (RR = 4.9, 95%CI, 1.1–21.3) significantly increased SPR, whereas SERM plus kallikrein increased sperm concentration (MD = 16.5 × 10⁶ mL–1, 95%CI, 1.6 × 10⁶–31.4 × 10⁶), and SERM plus CoQ10 significantly improved sperm progressive motility (MD = 11.3%, 95%CI, 7.3%–15.4%) and normal morphology (MD = 11.2%, 95%CI, 5.4%–16.9%) in men with oligoasthenozoospermia (OA). In terms of side effects, fatty acids and pentoxifylline were associated with foul breath and/or a bad taste (RR = 8.1, 95%CI, 1.0–63.5) and vomiting (RR = 8.0, 95%CI, 1.0–63.0), respectively. In conclusion, the optimal treatment for male infertility for live birth is still unknown. Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in couples with men with OA, respectively. The efficacy of other treatments on pregnancy outcomes warrants further verification.
... Coenzyme Q10 is a redox lipid, ubiquitously expressed in mammalian cells, able to promote energy generation via exchange of electrons and protons in the electron transport chain of internal mitochondrial membrane (Carocho and Ferreira, 2013;Lewin and Lavon, 1997;Patel and Sigman, 2008). It is also a potent antioxidant present in lipoproteins, capable to prevent lipid peroxidation by inhibiting the formation of hydroperoxides (Alleva et al., 1997;Bentinger et al., 2007;Carocho and Ferreira, 2013;Lewin and Lavon, 1997;Patel and Sigman, 2008). Coenzyme Q10 has been shown to improve stallion semen cooling (Nogueira, 2015;Yousefian et al., 2014), and subfertility in man by preventing lipid peroxidation and promoting sperm motility and DNA integrity (Agarwal and Majzoub, 2017;Talevi et al., 2013). ...
Article
This study aimed to evaluate the antioxidant properties of coenzyme Q10 (CoQ10) during cryopreservation of semen obtained from stallions having good and bad semen freezing ability (GFA vs. BFA, respectively). Forty ejaculates (n = 20 stallions) were split into five centrifugation and five freezing extenders containing different concentrations of CoQ10 (0, 25, 50, 75 and 100 μmols/L). If CoQ10 was added to the centrifugation extender, the freezing extender had no CoQ10 added; similarly, if CoQ10 was added to the freezing extender, the centrifugation extender had no CoQ10. Semen cryopreserved on extenders containing no CoQ10 served as the control. After post-thaw total sperm motility (TM) assessments, the stallions were classified as GFA (i.e., decrease of ≤25% in TM, n = 7) or BFA (i.e., decrease of ≥40% in TM, n = 5). Stallions not fitting (n = 8) this enrollment criteria had samples discarded. After that, two straws for each extender were thawed at 37 °C for 30 s; one straw was immediately used for evaluation of sperm kinetics, plasma membrane integrity, non-capacitated spermatozoa, reactive oxygen species production, mitochondrial activity and lipid peroxidation. The second straw was kept at 37 °C for 30 min and subjected to the same assessments. Expectedly, sperm motility parameters were significantly lower for stallions with BFA. There were no effects of CoQ10 concentration or time for all parameters evaluated in the group with GFA when compared with the control extender (p > 0.05), except lipid peroxidation (p < 0.05). However, stallions with BFA had improved sperm parameters for samples processed with extenders containing CoQ10 (particularly 75 μmols/L) (p < 0.05), except for the reactive oxygen species production and mitochondrial potential (T0) in which there were no differences between the groups (p > 0.05). In summary, 75 μmols/L appears to be the optimal dose of Co-Q10, particularly, when added to the centrifugation extender.
... Coenzyme Q 10 (CoQ10) is an endogenous lipid-soluble antioxidant that regulates the mitochondrial electron transport in the respiratory chain and the permeability of outer mitochondrial membrane [100]. CoQ10 also protects against oxidative stress thanks to its ability to inhibit hyperoxide formation, as shown by the correlation between CoQ10 concentration and H 2 O 2 levels [101]. ...
Article
Introduction: Infertility is one of the great challenges of modern healthcare. It afflicts about 8–12% of reproductive-aged couples worldwide, but the prevalence is even higher in industrialized countries. In 50% of cases, a male factor of infertility underlies the problem, but in about 30% of these cases the etiology of male infertility remains unknown. This eventuality, called idiopathic infertility, requires empirical medical therapy and/or assisted reproductive techniques. Areas covered: This article reviews the literature about the medical treatments available for idiopathic male infertility. These treatments can be divided into two main categories: hormonal therapies and non-hormonal therapies. The compounds with the strongest evidence of efficacy and the most used in clinical practice for the treatment of idiopathic male infertility are follicle-stimulating hormone (FSH) and estrogen receptor selective modulators (SERMs). Non-hormonal treatments include a series of compounds with antioxidant and prokinetic properties, supported by variable degrees of evidence of clinical efficacy. Expert opinion: Patients with idiopathic infertility have peculiar clinical features that differentiate them from each other. Therapy must, therefore, be personalized to each patient. Furthermore, scientific research must investigate the pathophysiological mechanisms that underlie infertility; only in this way, new targeted therapies can be developed.
... A very strong relationship has been described to occur between sperm count, motility, and ubiquinol concentration in seminal fluid [95]. ...
Chapter
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Nutritional utilization of antioxidants, such as vitamins C, E, ß-Carotene and micronutrients, such as folate and zinc, have been shown to be critically essential for normal semen quality and reproductive function. However, it is still, a large knowledge gap exists concerning the role of antioxidants on semen parameters and the role in treatment of male subfertility. Therefore, the current review article designed to find out the positive effect of antioxidants on semen quality, alterations in physiological functions of spermatozoa and infertility treatment It is advisable that patients with oxidative DNA disruption should be asked to take a simple course of antioxidants prior to undertaking assisted reproduction treatment (ART). In conclusion, antioxidant may be employed as a potent antioxidant and may improve infertility treatment outcomes with ART.
... An important correlation between sperm concentration, motility and seminal fluid ubiquinol-10 content has been found, whereas in total fluid, an inverse correlation between ubiquinol/ubiquinone ratio and the severity of teratozoospermia has been reported. These findings indicate that ubiquinol-10 impedes hydroperoxide occurrence in seminal fluid and in seminal plasma [70]. ...
Chapter
Full-text available
Oxidative stress (OS) has been recognized as an important cause of male infertility because it may damage sperm function and DNA integrity. Since antioxidants counteract the action of OS, these compounds are used in the medical treatment of male infertility. This chapter reviews the effects of the main antioxidants used in clinical practice. We used an evidence-based medicine criterion in the attempt to identify the molecules that have the highest clinical efficacy. Some antioxidants have been clearly shown to be effective by many well-conducted studies. These include vitamins C and E, carnitines and coenzyme Q10, which may be considered as a first line treatment. Other molecules, such as glutathione, zinc, lycopene and myoinositol, may be proposed as a second line treatment because their use is supported by a few, but well-designed studies. Lastly, the efficacy of other antioxidants, such as picnogenol, pentoxyfilline, etc., is not yet supported by a sufficient number of studies.
... However, lycopene has not been detected in semen [49]. Ubiquinol, found within seminal plasma, is the reduced form of coenzyme Q 10 and has been associated with lower levels of ROS and a corresponding increase in sperm count and motility [52]. ...
Article
Full-text available
Objectives To review the literature and provide an updated summary on the role of reactive oxygen species (ROS) in male infertility. Methods A review of PubMed, Cochrane review, and Web of Science databases for full-text English-language articles published between 1943 and 2017 was performed, focusing on the aetiology of ROS, physiological role of ROS on spermatic function, pathological role of ROS in infertility, evaluation of ROS, and role of antioxidants in oxidative stress. Results ROS play a role in spermatic function and fertilisation. The literature describes both a physiological and a pathological role of ROS in fertility. A delicate balance between ROS necessary for physiological activity and antioxidants to protect from cellular oxidative injury is essential for fertility. Conclusion Although elevated levels of ROS are implicated as a cause of infertility, there is no consensus on selecting patients to test for ROS, which test to perform, or if treatment for ROS can have a positive impact on infertility rates and pregnancy.
... Light thrown on the ability of antioxidant to reduce male infertility and investigate whether antioxidant supplementation to infertile men with can enhances seminal indices. Ubiqunone-10 was one of various compound that tested due to its role in energy metabolism and antioxidant status via its function as a liposoluble chain-breaking for lipoproteins and cell membranes 6 .Considerable amount of Ubiqunone-10 present in seminal plasma and spermatozoa to reduces oxidative stress and protect sperm viability 9 ,Seminal plasma Ubiqunone-10 concentration is significantly related with sperm number and motility 10 . The present study aimed to assessment ability of Ubiqunone-10 to achieve recovery of procarbazine-induced infertility in a male rat . ...
Article
Procarbazineis cytotoxic chemotherapy drug with obvious deleterious effects on male fertility. The present study aimed to investigate protective method via co-administration of Ubiquinone-10 with procarbazine to reduce harmful effects of procarbazine. Twenty-eight adult healthy male rats (3 months in age and weighing 250-300g) were randomly divided into four equal groups as following: animals of first group were received propylene glycol 20% orally and phosphate-buffered saline solution (PBS) intraperitoneally as control group while of second , third and fourth group were received procarbazine (30mg/ kg), Ubiqunone-10 (10 mg/kg) and combination of Ubiqunone-10 with procarbazine respectively, all treatments were lasted for 9 weeks. Results revealed that procarbazine induces significant increase in serum FSH and LH level while Testosterone level was significantly decreased .Similar decrease were also noticed in levels of glutathione (GSH) ,as well as activity of catalase (CAT) and superoxide dismutase (SOD) in testis. Moreover, procarbazine caused significant decrease in sperm count, motility and viability and significant increase in sperm abnormality. On the other hand, Co-administration of Ubiqunone-10 with procarbazine lead to ameliorate levels of hormone as well as to improve testicular catalase activity in addition to glutathione and superoxide dismutase levels.
... This passes into the mitochondria 800 to 1,200 times more than exogenous CoQ10. CoQ10 or ubiquinone passages electrons from complexes I and II to complex III in the mitochondrial respiratory chain (Carocho and Ferreira, 2013) and protects the mitochondria from oxidative damage due to its powerful antioxidant activity (Alleva et al., 1997). Therefore, our hypothesis is that supplementation of MitoQ in the vitrification medium might ameliorate the mitochondrial functionality in the vitrified spermatozoa. ...
Article
Full-text available
Mitochondria-targeted antioxidants have great potential to counterbalance the generated reactive oxygen species (ROS) because they cross the inner membrane of the mitochondria. Still, their use was not reported in vitrified human spermatozoa. Our laboratory has successfully vitrified spermatozoa without the use of permeable cryoprotectants, but subcellular-level evidence was missing. Therefore, this study aimed to improve spermatozoa vitrification using a mitochondria-targeted antioxidant (mitoquinone, MitoQ), reveal ultrastructural changes in the spermatozoa due to the use of a permeable cryoprotectant, and report alterations of functional proteins during the spermatozoa vitrification process. For this, each of 20 swim-up-prepared ejaculates was divided into seven aliquots and diluted with a vitrification medium supplemented with varying concentrations of MitoQ (0.02 and 0.2 μM), glycerol (1, 4, and 6%), and a combination of MitoQ and glycerol. All aliquots were vitrified by the aseptic capillary method developed in our laboratory. The spermatozoa function assays revealed that the addition of either MitoQ (0.02 μM), glycerol (1%), or a combination of MitoQ (0.02 μM) and glycerol (1%) in the vitrification medium results in better or equivalent spermatozoa quality relative to the control. Transmission electron microscopy revealed that MitoQ protects the spermatozoa from undergoing ultrastructural alterations, but glycerol induced ultrastructural alterations during the vitrification process. Next, we performed label-free quantitative proteomics and identified 1,759 proteins, of which 69, 60, 90, and 81 were altered in the basal medium, 0.02 μM MitoQ, 1% glycerol, and Mito-glycerol groups, respectively. Actin, tubulins, and outer dense fiber proteins were not affected during the vitrification process. Some of the identified ubiquitinating enzymes were affected during spermatozoa vitrification. Only a few proteins responsible for phosphorylation were altered during vitrification. Similarly, several proteins involved in spermatozoa–egg fusion and fertilization (IZUMO1 and Tektin) were not affected during the vitrification process. In conclusion, MitoQ attenuates the vitrification-induced ultrastructural changes and alterations in the key proteins involved in spermatozoa functions and fertilization.
... This passes into the mitochondria 800 to 1,200 times more than exogenous CoQ10. CoQ10 or ubiquinone passages electrons from complexes I and II to complex III in the mitochondrial respiratory chain (Carocho and Ferreira, 2013) and protects the mitochondria from oxidative damage due to its powerful antioxidant activity (Alleva et al., 1997). Therefore, our hypothesis is that supplementation of MitoQ in the vitrification medium might ameliorate the mitochondrial functionality in the vitrified spermatozoa. ...
... Lower levels of this molecule have been associated with higher concentrations of organic peroxides in seminal plasma. [9] A meta-analysis of three double-blind randomized clinical trials in 2013 showed a significant improvement in all semen parameters of men receiving CoQ10, without any effect on pregnancy rate. LBR was not examined. ...
Article
Full-text available
Livestock manures and composts can be contaminated by Mycobacterium avium subsp. paratuberculosis (MAP) which can cause paratuberculosis – Johne’s disease, an intestinal infection of domestic and wild ruminants. Therefore the inactivation of inoculated MAP ATCC 43015 in the compost and in the manure in storage was carried out. MAP (2.0 x 106/g) was inoculated into the compost in three actively ventilated and isolated vessels and in a conventional manure storage pile. Herrold’s Egg Yolk medium with supplements for MAP growth, followed by IS900 PCR for isolate identification was used. Direct PCR assessment of the persistence of sequence IS900 in the compost and manure material in parallel was implemented. Moisture, ash and ammonia content in the compost and manure specimens were determined and pH was measured. Salmonella enterica serovar Senftenberg (S. Senftenberg) was introduced into the compost and manure materials to demonstrate the hygienisation process. The presence of MAP on the growing culture media was confirmed in the samples 16 and 24 hours after exposure in compost and manure, respectively. No MAP was isolated on the medium after 24 hours of exposure. However, using the PCR assay of compost specimens, persistence of MAP was proved in the compost samples until day 7 and in the manure in storage even after 21 days of exposure. S. Senftenberg S-73/98 was not present 24 hours after exposure either in compost or manure storage.
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.
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The aim of this study was to evaluate the presentation of corticotrophinoma in regard to its size and ACTH production in cross-breed and pure breed dogs. A retrospective study based on clinical histories from 2003-2008 was carried out on dogs with confirmed Pituitary Dependent Hypercortisolism (PDH) (n=100). Evaluation of the pituitary was performed by nuclear magnetic resonance imaging (NMRI) and tumours were classified according to their projection with respect to the sella turcica as intrasellar (IS) or extrasellar (ES). 26% (26/100) of the evaluated patients were cross-breeds and 74% (74/100) were dogs of different pure breeds. Both ACTH plasma concentration and urinary cortisol/creatinine ratio did not show significant differences between pure breed and cross-breed dogs. With regard to the frequency of presentation of 13 and ES adenomas, no significant differences were observed neither between cross-breed and pure breed dogs nor between the different breeds studied. Thus, it can be concluded that there is no breed predilection for the presentation of IS or ES adenomas in dogs with PDH.
Article
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Coenzyme Q (CoQ10) is one of the most promising compounds in antioxidant therapy, due to its key role in mitochondria and its antioxidant action. It has been shown to have positive effects in the treatment of many diseases in humans. In contrast, there are only a limited number of studies and experimental data on CoQ10 supplementation in dogs. In the present study, changes of plasma CoQ10, serum total antioxidant capacity (TAC), and selected haematological and biochemical parameters were followed over 24 hours in healthy beagle dogs, following the administration of a single oral dose of 30 mg of water-soluble CoQ10. Correlations between plasma CoQ10 and serum TAC, and between TAC and albumin, a potent plasma antioxidant, were also investigated. A statistically significant increase of plasma CoQ10 was demonstrated as early as 20 minutes after CoQ10 administration, with a peak value four hours after administration. Contrary to expectation, simultaneous increases of plasma CoQ10 and TAC were not observed, however, a positive, statistically significant correlation between the latter two parameters was observed one hour after the administration of CoQ10 (p = 0.011), indicating a contribution of CoQ10 to the TAC of canine serum. The correlation, now close to statistical significance (p = 0.052), remained when plasma CoQ10 reached its peak value. The positive, statistically significant correlations between albumin and serum TAC, determined at basal measurements and 40 minutes and 1, 4 and 6 hours later, indicate a significant contribution of albumin to the TAC of canine serum. Selected haematological and biochemical parameters over 24 hours showed the diurnal variations normally found in dogs. Further investigation is needed to establish the influence of long-term CoQ10 supplementation on TAC in dogs.
Chapter
Coenzyme Q (CoQ) is a ubiquitous lipidic molecule located in all cell membranes and lipoproteins in blood plasma. Its phenolic head gives it the capacity to accept and donate electrons. For this reason, it is the main lipidic redox compound in cells. This property permits CoQ to take part in the mitochondrial electron transfer chain and in many other activities in mitochondria, and also to act as the major antioxidant in the lipid environment of the organism. During aging, the endogenous synthesis of CoQ decreases. Due to its central function, this decrease can affect many metabolic, signaling, and antioxidant activities, probably severely influencing aging progression. Further, CoQ depletion has been also associated with many aging-associated and metabolic diseases. This chapter revises the importance of this key molecule in cell physiology and aging progression.
Article
Both the bioenergetic and the antioxidant role of CoQ(10) suggest a possible involvement in sperm biochemistry and male infertility. CoQ(10) can be quantified in seminal fluid, where its concentration correlates with sperm count and motility. It was found that distribution of CoQ(10) between sperm cells and seminal plasma was altered in varicocele patients, who also presented a higher level of oxidative stress and lower total antioxidant capacity. The effect of vericocelectomy on partially reversing these biochemical abnormalities is discussed. The redox status of coenzyme Q(10) in seminal fluid was also determined: an inverse correlation was found between ubiquinol/ubiquinone ratio and hydroperoxide levels and between this ratio and the percentage of abnormal sperm forms. After the first in vitro observations CoQ(10) was administered to infertile patients affected by idiopathic asthenozoospermia, originally in an open label study and then in three randomized placebo-controlled trials; doses were around 200-300 mg/day and treatment lasted 6 months. A significant increase in the concentration of CoQ(10) was found, both in seminal plasma and sperm cells. Treatment also led to a certain improvement in sperm motility. In one of the studies there was also a decrease in plasma levels of follicle stimulating horhone (FSH) and luteinizine horhone (LH). Administration of CoQ(10) may play a positive role in the treatment of asthenozoospermia, possibly related to not only to its function in the mitochondrial respiratory chain but also to its antioxidant properties. Further studies are needed in order to determine whether there is also an effect on fertility rate.
Article
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The reactive oxygen species, the highly reactive metabolites of oxygen, play a crucial role in both the normal function and the metabolism of sperm cells. Oxygen radicals achieve their physiological effects in the cells only if there is a proper balance between their production and degradation. In case of radicals' production exceeding the antioxidant capacity of the semen, there is an oxidative damage of the membrane lipids and proteins as well as the DNA damage followed by the fragmentation and decondensation of DNA. The ejaculates were obtained from seventy-seven infertile and fertile healthy individuals. The semen samples were collected and classified according to the WHO criteria. The activities of superoxide dismutase and catalase as well as the concentration of malondialdehyde were measured spectrophotometrically. The fertile, healthy donors showed the significantly higher activities of both superoxide dismutase and catalase, as well as the lower concentration of malondialdehyde compared to the infertile donors. The activities of superoxide dismutase and catalase, as well as the HOS test, correlated positively with the sperm cell number, but negatively with the concentration of malondialdehyde. The activity of superoxide dismutase and the concentration of malondialdehyde were highest in the group of patients with the lowest success of the HOS test. The assessment of the antioxidant enzymes and malondialdehyde in addition to the semen analysis and the HOS test may be greatly useful in diagnosing infertility in men having oxidative stress in their etiology.
Chapter
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For a number of years, coenzyme Q (CoQ10 in humans), was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in plasma, and also extensively investigated its antioxidant role. This chapter discusses the relationship between the acknowledged bioenergetic role of CoQ10 and some clinical effects. The antioxidant properties of CoQ10 are then analyzed especially for their consequences on protection of circulating human low-density lipoproteins and prevention of atherogenesis. The relationship between CoQ10 and statins is also discussed in the light of possible involvement of CoQ10 deficiency in the issue of statin side effects. New aspects of the antioxidant involvement of coenzyme Q are also discussed together with their relevance in cardiovascular disease. Data are reported on the efficacy of CoQ10 in ameliorating endothelial dysfunction in patients affected by ischemic heart disease. Many of the effects of CoQ10, which were classically ascribed to its bioenergetic properties, are now considered as the result of its biochemical interaction with nitric oxide (NO), NO synthase and reactive oxygen species capable of inactivating NO. Clinical studies are reported highlighting the effect of CoQ10 on extracellular SOD, which is deeply involved in endothelial dysfunction. Previous studies have shown decreased levels of CoQ10 in the seminal plasma and sperm cells of infertile men with different kinds of asthenospermia. Research has been extended to supplementation with CoQ10 of infertile men affected by idiopathic asthenozoospermia. CoQ10 levels increased significantly in seminal plasma and sperm cells after 6 months of treatment with concomitant improvement of sperm cell motility.
Article
DNA fragmentation is an important factor in the aetiology of male infertility. However, it is still underevaluated and its inclusion in routine semen analysis is debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. Couples may be counselled to proceed directly to intracytoplasmic sperm injection as it is more successful in this group, avoiding costly procedures, recurrent failures or pregnancy losses; however, this treatment is not without limitations or risks. Ideally DNA fragmentation should be minimized where possible. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed, and in many cases are shown to be easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential functions, including fertilization. Reducing oxidative stress may improve a couple’s chances of conception either naturally or via assisted reproduction. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible.
Article
Improving sire reproductive performance in artificial insemination (AI) programs and maximizing the use of sires with valuable genomes are high on the list of priorities for livestock breeders in the United States and worldwide. While fixed-time AI and accurate estrous detection have already ameliorated the reproductive management of cows and sows, substantial gains remain to be made in the selection and utilization of male animals for field AI. In addition to better, more objective evaluation of breeding soundness and semen quality, numbers of spermatozoa per AI dose could be reduced and numbers of AI doses per collection could be increased without sacrificing conception rates if the fittest spermatozoa can be purified from raw semen and protected from adverse effects of dying and decaying spermatozoa present in both the fresh and the extended semen. The present article reviews recent progress in methodology for semen purification, including nanopurification and semen/extender supplementation with antioxidants.
Chapter
Oxidative stress (OS) has been recognized as one important cause of male infertility because it may damage sperm function and DNA integrity. Since antioxidants counteract the action of OS, these compounds are used in the medical treatment of male infertility. This chapter reviews the effects of the main antioxidants used in the clinical practice. We applied an evidence-based medicine criterion in the attempt to identify the molecules provided with the most effective action. Some antioxidants have been clearly shown to be effective by many well-conducted studies. These include vitamins C and E and carnitines which may be considered as a first-line treatment. Other molecules, such as glutathione and coenzyme Q10, may be proposed as a second-line treatment because their use is supported by few but well-performed studies. Lastly, the efficacy of other antioxidants, such as pycnogenol, lycopene, etc., is not yet supported by a sufficient number of studies.
Chapter
An excess of reactive oxygen species (ROS) and other oxidant radicals has been associated with male infertility. The total oxyradical scavenging capacity (TOSC) is a recently developed assay measuring the overall capability of biological fluids or cellular antioxidants to neutralize the toxicity of various oxyradicals. The TOSC assay can discriminate between different forms of ROS, allowing to identify the role of specific antioxidants, or their pathway of formation in the onset of toxicological or pathological processes. The previous application of TOSC assay in andrology led us to show a reduced antioxidant efficiency in seminal fluid of infertile men with a significant correlation between the scavenging capacity towards hydroxyl radicals and parameters of sperm cell motility. Despite the fact that oxidative stress is well recognized as a cause of male infertility, the use of antioxidants as a treatment is still debated, and it is considered as a “supplementation” therapy, rather than an etiological or physiopathological therapy, since no clear correlation has been investigated between a real deficiency of a specific antioxidant and the effect of oral supplementation. Various models have been introduced to explore the protective role of different antioxidants in vitro, and some differences can be discovered regarding the protective effects exerted by specific enzymatic or non-enzymatic molecules. We focus our attention on two main natural antioxidants, the efficacy of which has been supported by clinical trials: coenzyme Q10 and carnitine.
Article
Study question: What is the relationship between sperm DNA fragmentation and oxidative stress (OS) with increasing male age? Summary answer: Sperm DNA fragmentation increases with age and is likely related to both defective spermatogenesis and increasing OS levels. What is known already: Sperm quality declines with age. The presence of DNA damage in a high fraction of spermatozoa from a raw semen sample is associated with lower male fertility in natural conception and intrauterine insemination. Study design, size, duration: A retrospective cohort study of 16 945 semen samples analysed at a single reference laboratory between January 2010 and December 2018. Participants/materials, setting, methods: All males were undergoing an infertility evaluation. The cohort was divided into seven age categories: <30, 30-34, 35-39, 40-44, 45-49, 50 to <54 and ≥55 years. The mean age was 37.6 years (SD 6.8). Sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) were calculated using flow cytometry. OS levels were measured using the oxidative stress adducts (OSA) test, by spectrophotometry. ANOVA with weighted polynomial contrast analysis was used to evaluate trends for DFI, OSA and HDS values across age categories. Main results and the role of chance: Mean DFI significantly increased across all age groups (Ptrend < 0.001). OSA was lowest in patients <30 years old (mean 3.6, SD 1.0) and also increased as age increased (Ptrend < 0.001). There was a statistically significant difference between age groups for each of the three parameters (P < 0.001). There was a significant linear trend for DFI, OSA and HDS across the seven age categories (P < 0.001). Among patients with high DFI, there was a decreasing age-dependent trend in the patients observed with high OSA (P < 0.001). Limitations, reasons for caution: This is a retrospective study. All males included in the study were undergoing a work-up for infertility and may not be representative of a fertile population. Additional patient demographics and clinical data were not available. Wider implications of the findings: DNA and/or oxidative damage in sperm may be just as important to understand as the chromosomal aberrations that are carried in the oocyte. Further studies are needed to evaluate the effect of advancing paternal age on the male genome and, ultimately, on the health of the offspring. Study funding/competing interest(s): No funding was obtained for this study. V.D. is an employee of Reprosource/Quest Diagnostics. D.S. reports he was a Scientific Advisor to Cooper Surgical. Trial registration number: N/A.
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.
Chapter
Chronic diseases including cancer, coronary heart disease, diabetes, and osteoporosis are the major cause of mortality all over the world. Many factors contribute to the risk of such chronic diseases including genetics, age, and environmental factors. Among the environmental factors, diet has emerged as one of the major contributing factors. High-calorie, high-fat, high-salt and -sugar, and low-fi ber diets are typically associated with the high risk of chronic diseases. Based on scientifi c data, dietary guidelines now recommend increased consumption of plant-based nutrients for the prevention of chronic diseases. Although both males and females are equally at risk, certain diseases such as prostate disorders, testicular problems, and impotency related to the sperm, are unique to men. The incidence of certain other diseases tends to be higher in men due to their lifestyle habits and advancing age. Genetic makeup, environmental factors, and diet also infl uence the incidence and patterns of human diseases in different regions of the world. Typically, infectious diseases were the main cause of mortality among the Asian, South American, and African population compared to the more industrialized Western and European population where chronic, metabolic diseases are more prevalent. However, such differences in human disease patterns are declining due to changes in lifestyle and dietary habits.
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We had previously demonstrated that Coenzyme Q10 [(CoQ10) also commonly called ubiquinone]is present in well-measurable levels in human seminal fluid, where it probably exerts important metabolic and antioxidant functions; seminal CoQ10 concentrations show a direct correlation with seminal parameters (count and motility). Alterations of CoQ10 content were also shown in conditions associated with male infertility, such as asthenozoospermia and varicocele (VAR). The physiological role of this molecule was further clarified by inquiring into its variations in concentrations induced by different medical or surgical procedures used in male infertility treatment. We therefore evaluated CoQ10 concentration and distribution between seminal plasma and spermatozoa in VAR, before and after surgical treatment, and in infertile patients after recombinant human FSH therapy. The effect of CoQ10 on sperm motility and function had been addressed only through some in vitro experiments. In two distinct studies conducted by our group, 22 and 60 patients affected by idiopathic asthenozoospermia were enrolled, respectively. CoQ10 and its reduced form, ubiquinol, increased significantly both in seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, at baseline and after treatment, of seminal plasma or intracellular CoQ10, ubiquinol levels and kinetic parameters was found in the treated group. Patients with lower baseline value of motility and CoQ10 levels had a statistically significant higher probability to be responders to the treatment. In conclusion, the exogenous administration of CoQ10 increases both ubiquinone and ubiquinol levels in semen and can be effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia
Article
The objective of the experiment was to evaluate the effect of the addition of different concentrations of the antioxidants Coenzyme Q10 (CoQ10) and melatonin to equine semen freezing diluent, alone or in combination, during the cryopreservation process. Twenty ejaculates (n = 5 stallions) were divided in groups: Control (C, without the addition of antioxidants), melatonin 0.75 mM (MEL1), melatonin 1.5 mM (MEL2), CoQ10 40 μg/mL (Q1), CoQ10 200 μg/mL (Q2), and CoQ10 40 μg/mL+ 0.75 mM melatonin (Q1 +MEL1). Q1 and Q2 groups demonstrated intact plasma membrane and high mitochondrial membrane potential after 30 (M-30) and 60 (M-60) min of incubation compared with the control group (Q1: 64.8 % ± 9.9 %, Q2: 65.2 % ± 10.5 %, C: 55.1 % ± 10.0 %; M-30 and Q1: 63.3 % ± 10.4 %, Q2: 64.6 % ± 10.8 %, C: 53.1 ± 10.6 %; M-60; P < 0.05). Melatonin conferred greater membrane stability at all evaluated times compared with the control group (MEL1: 42.1 % ± 6.0 %; MEL2: 44.0 % ± 6.7 %, C: 35.9 % ± 5.9 %; M-0; MEL1: 40.8 % ± 5.6 %; MEL2: 42.6 % ± 7.2 %, C: 33.1 % ± 6.6 %; M-30 and MEL1: 37.5 % ± 7.4 %; MEL2: 39.1 % ± 7.2 %; C: 31.3 % ± 6.5 %; M-60; P < 0.05). The use of antioxidants alone or in combination resulted in lower levels of lipoperoxidation at all times evaluated compared with in the control group (P < 0.05). In conclusion, CoQ10 and melatonin were effective in the cryopreservation of equine semen by decreasing lipoperoxidation and promoting a higher percentage of spermatozoa with a high mitochondrial potential, total and progressive motility, and prevention of membrane lipid disorder.
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.
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Coenzyme Q10 (CoQ10) is an efficient antioxidant produced endogenously in a living organism. It acts as an important cofactor in the electron transport system of mitochondria and reported as a safe supplement in humans and animals with minimal adverse effect. CoQ10 is found naturally, as a trans configuration, chemical nomenclature of which is 2,3- dimethoxy-5- methyl-6-decaprenyle -1,4-benzoquinone. It is found in the body in two forms. In quinone form (oxidized form), it serves as an electron transporter that transfers the electrons in the electron transport chain between various complexes, and in ubiquinol form (reduced form), it serves as potent antioxidants by scavenging free radicals or by tocopherol regeneration in the living organism. Its primary roles include synthesis of adenosine triphosphate (ATP), stabilizes lipid membrane, antioxidant activity, cell growth stimulation, and cell death inhibition. CoQ10 has shown a variety of pharmacological and clinical effects including neuroprotective, hepatoprotective, anti-atherosclerotic, anticonvulsant, antidepressant, anti-inflammatory, antinociceptive, cardiovascular, antimicrobial, immunomodulatory, and various effects on the central nervous system. Present review has set about to bring updated information regarding to clinical and preclinical activities of CoQ10, which may be helpful to researchers to explore a new bioactive molecules for various therapeutic application.
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Recent studies have demonstrated that human spermatozoa are capable of generating reactive oxygen species and that this activity is significantly accelerated in cases of defective sperm function. In view of the pivotal role played by lipid peroxidation in mediating free radical damage to cells, we have examined the relationships between reactive oxygen species production, lipid peroxidation, and the functional competence of human spermatozoa. Using malondialdehyde production in the presence of ferrous ion promoter as an index of lipid peroxidation, we have shown that lipid peroxidation is significantly accelerated in populations of defective spermatozoa exhibiting high levels of reactive oxygen species production or in normal cells stimulated to produce oxygen radicals by the ionophore, A23187. The functional consequences of lipid peroxidation included a dose-dependent reduction in the ability of human spermatozoa to exhibit sperm oocyte-fusion, which could be reversed by the inclusion of a chain-breaking antioxidant, alpha-tocopherol. Low levels of lipid peroxidation also had a slight enhancing effect on the generation of reactive oxygen species in response to ionophore, without influencing the steady-state activity. At higher levels of lipid peroxidation, both the basal level of reactive oxygen species production and the response to A23187 were significantly diminished. In contrast, lipid peroxidation had a highly significant, enhancing effect on the ability of human spermatozoa to bind to both homologous and heterologous zonae pellucidae via mechanisms that could again be reversed by alpha-tocopherol. These results are consistent with a causative role for lipid peroxidation in the etiology of defective sperm function and also suggest a possible physiological role for the reactive oxygen species generated by human spermatozoa in mediating sperm-zona interaction.
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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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Recent studies have demonstrated that human spermatozoa are capable of generating reactive oxygen species and that this activity is significantly accelerated in cases of defective sperm function. In view of the pivotal role played by lipid peroxidation in mediating free radical damage to cells, we have examined the relationships between reactive oxygen species production, lipid peroxidation, and the functional competence of human spermatozoa. Using malondialdehyde production in the presence of ferrous ion promoter as an index of lipid peroxidation, we have shown that lipid peroxidation is significantly accelerated in populations of defective spermatozoa exhibiting high levels of reactive oxygen species production or in normal cells stimulated to produce oxygen radicals by the ionophore, A23187. The functional consequences of lipid peroxidation included a dose-dependent reduction in the ability of human spermatozoa to exhibit sperm oocyte-fusion, which could be reversed by the inclusion of a chain-breaking antioxidant, alpha-tocopherol. Low levels of lipid peroxidation also had a slight enhancing effect on the generation of reactive oxygen species in response to ionophore, without influencing the steady-state activity. At higher levels of lipid peroxidation, both the basal level of reactive oxygen species production and the response to A23187 were significantly diminished. In contrast, lipid peroxidation had a highly significant, enhancing effect on the ability of human spermatozoa to bind to both homologous and heterologous zonae pellucidae via mechanisms that could again be reversed by alpha-tocopherol. These results are consistent with a causative role for lipid peroxidation in the etiology of defective sperm function and also suggest a possible physiological role for the reactive oxygen species generated by human spermatozoa in mediating sperm-zona interaction.
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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.
Article
Objective To determine the incidence of reactive oxygen species formation in semen of a population of patients consulting for infertility. Design The incidence of reactive oxygen species formation in whole semen and in washed spermatozoa was studied. The values obtained were correlated with semen parameters. The effect of the type of sperm washing on reactive oxygen species formation was also investigated. Setting Semen samples from patients consulting for infertility and control subjects were obtained by masturbation after 3 days of sexual abstinence. Reactive oxygen species formation was measured in whole semen, sperm suspension washed by Percoll gradients, or repeated centrifugations. Sperm motility parameters were measured by computer-aided sperm analysis. Patients, Participants Fertile control men and an unselected population of patients consulting for infertility. Interventions None. Main Outcome Measure Reactive oxygen species formation by fresh semen specimen or washed spermatozoa was measured in a computer-driven LKB 1251 Luminometer (LKB-Wallac, Turku, Finland). Results Reactive oxygen species formation was detected in 40% of the semen with spermatozoa from infertile patients, whereas none was found in 6 azoospermic men and 10 control men. The level of reactive oxygen species formation was inversely correlated to the semen volume, the percentage of motile spermatozoa, and sperm linearity both in semen and in Percoll-washed spermatozoa. Washing by repeated centrifugation-resuspension increased 20- to 50-fold sperm reactive oxygen species formation. This enhancement was caused by the centrifugation itself and by the removal of seminal plasma. Both morphologically normal and abnormal spermatozoa produced reactive oxygen species. Conclusion The data suggest that reactive oxygen species formation by spermatozoa may be a significant cause for male infertility.
Article
To determine the incidence of reactive oxygen species formation in semen of a population of patients consulting for infertility. The incidence of reactive oxygen species formation in whole semen and in washed spermatozoa was studied. The values obtained were correlated with semen parameters. The effect of the type of sperm washing on reactive oxygen species formation was also investigated. Semen samples from patients consulting for infertility and control subjects were obtained by masturbation after 3 days of sexual abstinence. Reactive oxygen species formation was measured in whole semen, sperm suspension washed by Percoll gradients, or repeated centrifugations. Sperm motility parameters were measured by computer-aided sperm analysis. Fertile control men and an unselected population of patients consulting for infertility. None. Reactive oxygen species formation by fresh semen specimen or washed spermatozoa was measured in a computer-driven LKB 1251 Luminometer (LKB-Wallac, Turku, Finland). Reactive oxygen species formation was detected in 40% of the semen with spermatozoa from infertile patients, whereas none was found in 6 azoospermic men and 10 control men. The level of reactive oxygen species formation was inversely correlated to the semen volume, the percentage of motile spermatozoa, and sperm linearity both in semen and in Percoll-washed spermatozoa. Washing by repeated centrifugation-resuspension increased 20- to 50-fold sperm reactive oxygen species formation. This enhancement was caused by the centrifugation itself and by the removal of seminal plasma. Both morphologically normal and abnormal spermatozoa produced reactive oxygen species. The data suggest that reactive oxygen species formation by spermatozoa may be a significant cause for male infertility.
Article
Mouse and human spermatozoa, but not rabbit spermatozoa, have long been known to be sensitive to loss of motility induced by exogenous H2O2. Recent work has shown that loss of sperm motility in these species correlates with the extent of spontaneous lipid peroxidation. In this study, the effect of H2O2 on this reaction in sperm of the three species was investigated. The rate of spontaneous lipid peroxidation in mouse and human sperm is markedly enhanced in the presence of 1-5 mM H2O2, while the rate in rabbit sperm is unaffected by H2O2. The enhancement of lipid peroxidation, the rate of reaction of H2O2 with the cells, the activity of sperm glutathione peroxidase, and the endogenous glutathione content are highest in mouse sperm, intermediate in human sperm, and very low in rabbit sperm. Inactivation of glutathione peroxidase occurs in the presence of H2O2 due to complete conversion of endogenous glutathione to GSSG: No GSH is available as electron donor substrate to the peroxidase. Inactivation of glutathione peroxidase by the inhibitor mercaptosuccinate has the same effect on rate of lipid peroxidation and loss of motility in mouse and human sperm as does H2O2. This implies that H2O2 by itself at 1-5 mM is not intrinsically toxic to the cells. With merceptosuccinate, the endogenous glutathione is present as GSH in mouse and human sperm, indicating that the redox state of intracellular glutathione by itself plays little role in protecting the cell against spontaneous lipid peroxidation. Mouse and human sperm also have high rates of superoxide production. We conclude that the key intermediate in spontaneous lipid peroxidation is lipid hydroperoxide generated by a chain reaction initiated by and utilizing superoxide. Removal of this hydroperoxide by glutathione peroxidase protects these sperm against peroxidation; inactivation of the peroxidase allows lipid hydroperoxide to increase and so increases the peroxidation rate. Rabbit sperm have low rates of superoxide reaction due to high activity of their superoxide dismutase; lack of endogenous glutathione and low peroxidase activity does not affect their rate of lipid peroxidation. As a result, these sperm are not affected by either H2O2 or mercaptosuccinate. These results lead us to postulate a mechanism for spontaneous lipid peroxidation in mammalian sperm which involves reaction of lipid hydroperoxide and O2 as the rate-determining step.
Article
Spontaneous lipid peroxidation in washed human spermatozoa was induced by aerobic incubation at 32 C and measured by malonaldehyde production; loss of motility during the incubation was determined simultaneously. Malonaldehyde production at the point of complete loss of motility, defined as the lipoperoxidative lethal endpoint (LLE), was 0.10 +/- 0.03 nmol/10(8) cells (mean +/- SD, n = 40), and was independent of the time to complete loss of motility. Human spermatozoa produced both H2O2 and O2-. during aerobic incubation. Inhibition of superoxide dismutase in these cells with KCN showed that all the H2O2 production is due to action of the dismutase. The superoxide dismutase activity of individual human sperm samples varied between 1 and 10 U/10(8) cells, variations between samples from a single donor being nearly as great as those between different donors. The time to complete motility loss (tL) showed equal variation of 1 to 10 hours among samples. The rate of spontaneous lipid peroxidation, calculated as LLE/tL, for a given sperm sample and the superoxide dismutase activity of the same sample, determined prior to aerobic incubation, gave a good linear correlation (r = 0.97). Glutathione reductase, glutathione peroxidase, and glutathione were found to be present in human spermatozoa, but showed little variation among samples. These results suggest that superoxide dismutase plays the major role in protecting human spermatozoa against lipid peroxidation. In addition, the superoxide dismutase activity of a fresh sperm sample appears to be a good predictor of the lifetime (up to the complete loss of motility) of that particular sample, and so may prove useful in semen analysis.
Article
The mechanisms responsible for mediating the influence of sperm preparation protocols on human sperm function have been investigated. Techniques that involved the separation of motile spermatozoa prior to centrifugation were found to yield sperm suspensions of highest quality. If the spermatozoa were centrifuged prior to isolation of the motile cells, sperm function was impaired. The detrimental effects of centrifugation were associated with a sudden burst of reactive oxygen species production by a discrete subpopulation of cells (characterized by significantly diminished motility and fertilizing capacity) that could be separated from normal functional spermatozoa on Percoll gradients. If unfractionated sperm suspensions were subjected to centrifugation, the reactive oxygen species generated by this subpopulation impaired the functional competence of normal spermatozoa in the same suspension. Assessment of the ability of the antioxidants, butylated hydroxytoluene, and vitamin E, to curtail the peroxidative damage inflicted by such cells in response to centrifugation revealed a significant improvement of sperm function in the presence of vitamin E.
Article
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.
Article
The effect of acute iron overload was studied in rat testes 20 h after a single administration of iron-dextran (500 mg/kg body wt, ip). Total testes iron content was 6.1-fold higher in iron-treated rats compared to controls. The endogenous level of lipid peroxidation was evaluated as 2-thiobarbituric acid-reactive substances (TBARS). Testes iron concentration (0.12-2.67 mumol/g of tissue) was positively correlated (r = 0.86; P < 0.01) with testes TBARS (26.2-77.5 nmol/g tissue). Testes content of lipid-soluble antioxidants, alpha-tocopherol, ubiquinol-9, and ubiquinol-10, were inversely correlated with testes iron content. The steady-state level of 8-oxo-7,8-dihydro-2'-deoxyguanosine in testes DNA was 25% higher (P < 0.01) in iron-treated rats compared to controls (2.4 +/- 0.2 oxo8dG/10(5)dG). The content of protein carbonyl groups (1.45 +/- 0.13 nmol/mg protein) and the activity of glutamine synthase (1.32 +/- 0.07 units/mg protein) were similar for the iron-treated and control rats. Fe treatment did not affect superoxide dismutase, catalase, and glutathione peroxidase activities. The results indicate that acute iron overload causes iron accumulation in rat testes, which is associated with increased lipid and DNA oxidative damage and depletion of lipid-soluble antioxidants.
Article
We describe the application of the FOX2 (ferrous oxidation in xylenol orange, version 2) method to the measurement of hydroperoxides in plasma. Authentic plasma hydroperoxides can be determined by a strategy in which the hydroperoxide reductant, triphenylphosphine, is used to discriminate between the background signal generated by ferric ions present in plasma and that generated by hydroperoxide in plasma. The approach was validated by extraction of total lipids from plasma using ethyl acetate prior to assay with the FOX2 reagent. Plasma from 23 normal individuals contained hydroperoxide in the range of 0.22 to 7.8 microM with a mean of 3.02 microM and a population standard deviation of 1.85 microM. After partitioning with ethyl acetate, plasma hydroperoxide levels ranged from 0.22 to 6.22 microM, with a mean value of 2.52 microM and a population standard deviation of 1.65 microM.
Article
Ubiquinone (coenzyme Q), in addition to its function as an electron and proton carrier in mitochondrial and bacterial electron transport linked to ATP synthesis, acts in its reduced form (ubiquinol) as an antioxidant, preventing the initiation and/or propagation of lipid peroxidation in biological membranes and in serum low-density lipoprotein. The antioxidant activity of ubiquinol is independent of the effect of vitamin E, which acts as a chain-breaking antioxidant inhibiting the propagation of lipid peroxidation. In addition, ubiquinol can efficiently sustain the effect of vitamin E by regenerating the vitamin from the tocopheroxyl radical, which otherwise must rely on water-soluble agents such as ascorbate (vitamin C). Ubiquinol is the only known lipid-soluble antioxidant that animal cells can synthesize de novo, and for which there exist enzymic mechanisms that can regenerate the antioxidant from its oxidized form resulting from its inhibitory effect of lipid peroxidation. These features, together with its high degree of hydrophobicity and its widespread occurrence in biological membranes and in low-density lipoprotein, suggest an important role of ubiquinol in cellular defense against oxidative damage. Degenerative diseases and aging may bc 1 manifestations of a decreased capacity to maintain adequate ubiquinol levels.
The antioxidant role of coenzyme Q
  • R E Beyer
  • K Nordenbrand
  • L Ernster
Role of CoQ10 in preventing peroxidation of LDL subfractions
  • Alleva