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Withania somnifera improves semen quality by combating oxidative stress and cell death and improving essential metal concentrations
Abstract
This study investigated the effect of a 3-month treatment with Withania somnifera on apoptosis and intracellular reactive oxygen species (ROS) concentration of spermatozoa and the metal ions copper, zinc, iron and gold in seminal plasma from infertile men (normozoospermic, n = 25; oligozoospermic, n = 25; and asthenozoospermic, n = 25). The apoptotic and necrotic cell distribution were analysed by annexin-V binding and propidium iodide uptake using flow cytometry. ROS generation was measured by fluorescence intensity and metal ions were analysed by atomic absorption spectrophotometry. The results demonstrated that, prior to treatment, sperm apoptosis and intracellular ROS concentrations were significantly higher in all groups of infertile men compared with controls (P < 0.01 to P < 0.001). Similarly, the concentrations of the essential metal ions Cu2+, Zn2+, Fe2+ and Au2+ in seminal plasma were lower. Treatment with W. somnifera significantly reduced apoptosis in normozoospermic and oligozoospermic men and ROS concentrations in oligozoospermic and asthenozoospermic men (all P < 0.05). Treatment also significantly improved metal ion concentrations in infertile men (P < 0.01). It is concluded that W. somnifera improves semen quality by reducing oxidative stress and cell death, as well as improving essential metal ion concentrations.
... However, the magnitude of changes did vary based on the infertility subtype being examined [e.g, asthenozoospermic (AZ), normozoospermic (NZ), and oligozoospermic (OZ)]. In a further analysis of semen samples collected in the Ahmad et al. (2010) study, it was revealed that ashwagandha intake at a dose of 5 g-a-day for 3 months was associated with reductions in reactive oxygen species (all groups) and apoptosis (NZ and OZ only) in spermatozoa, and increases in concentrations of the metal ions zinc, iron, and gold (all groups), and copper (NZ and OZ only) (Shukla et al., 2011). In a 12-week, randomised, double-blind, placebo-controlled study on 46 infertile men, 675 mg daily of an ashwagandha root extract (KSM-66®) was associated with significant increases in sperm concentration, semen volume, sperm motility, serum testosterone, and luteinising hormone although no statistically-significant changes occurred in the placebo group (Ambiye et al., 2013). ...
... An overall low risk of bias was identified for 22 of the 35 randomised, controlled trials. Four studies examining the effects of ashwagandha on sexual function and fertility (Ahmad et al., 2010;Gupta et al., 2013;Mahdi et al., 2009;Shukla et al., 2011), one on fatigue (Biswal et al., 2013), and one on hypercholesterolemia/diabetes (Andallu and Radhika, 2000) were open-label/case series trials and risk of bias analyses are detailed in supplementary file 1 ( Table 2). Most of these studies exhibited some risk of bias concerns. ...
... (Auddy et al., 2008) There were no dropouts due to adverse effects (Andrade et al., 2000) 2 adverse effects reported in ASH group and 3 in PL. No further details provided Sexual function and fertility (Nasimi Doost Azgomi et al., 2018a) Not reported (Dongre et al., 2015) No reported adverse effects reported by participants (Ambiye et al., 2013) Not reported (Gupta et al., 2013) Not reported (Mamidi and Thakar, 2011) Not reported (Ahmad et al., 2010;Shukla et al., 2011) Not reported (Mahdi et al., 2009) Not reported ...
Ashwagandha is a medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. Because interest and the popularity of ashwagandha has increased in several Western countries, there are an increasing number of human trials evaluating its efficacy across a range of conditions. Based on the PRISMA guidelines, human trials assessing the effects of ashwagandha on mental and/or physical conditions, and/or human performance, used as a stand-alone or adjunct intervention, and delivered as a single ingredient, were eligible for inclusion in this systematic review. Forty-one studies were identified examining the effects of ashwagandha on stress and anxiety, sexual function and fertility, athletic performance, cognitive performance, pain, fatigue, thyroid function, schizophrenia, diabetes, obsessive-compulsive disorder, insomnia, hypercholesterolemia, and tuberculosis. Results from most of these studies indicated positive effects from ashwagandha intake, although treatment dose, duration, and extract types varied significantly. Moreover, trials often comprised of small sample sizes and were primarily conducted in India (32 studies). Overall, the strongest evidence for therapeutic efficacy of ashwagandha is the alleviation of stress and anxiety symptoms. The results from this systematic review suggest ashwagandha has a potentially large array of therapeutic applications. However, while promising, the significant heterogeneity across studies and the limited number of investigations means further research utilising robust and adequately-powered study designs are required.
... WS has pharmacological relevance in innumerable ways. It is evident through various studies that WS has antioxidant activities and can inhibit LPO in spermatozoa [44], which may be a prime factor for the disruption of sperm functions and in idiopathic male infertility. WS reportedly could ameliorate and restore the levels of sex hormones in infertile men with psychological and/or physiological stress. ...
... The daily administered daily of WS root powder at a dose of 5 g per day could decrease ROS generation in the seminal plasma and improved sperm count in infertile men with normozoospermia [44]. Several studies have conveyed the effects of WS on semen quality in infertile men and enzymatic antioxidant activities. ...
... Several studies have conveyed the effects of WS on semen quality in infertile men and enzymatic antioxidant activities. It has been shown that WS could reduce the level of LPO as compared with the pretreatment group [44][45][46]. WS could act by donating electrons and inhibiting the consequent destructive chain reaction mediated by free radicals, thereby reducing the overall ROS burden [31]. ...
Herbal medicines have been used in the treatment of male infertility since ancient times and are steadily regaining their popularity in recent decades. Studies on the efficacy of herbal medicine seem to be a rediscovery of traditional medicinal practices. This chapter discusses the various pharmacological effects of Withania somnifera, Panax ginseng, and Centella asiatica on semen quality and male reproductive hormones. The mechanism of actions of these herbs are discussed to highlight their effects on male reproduction. Future studies on male fertility treatment will need to further explore the synergistic effects of these herbal extracts with that of standard medicines. Additionally, studies focusing on the use of herbal components in ART would be beneficial to further develop the field. The efficacy of treatment in male infertility patients may be improved with advancements in herbal research, use of medical and herbal therapy in combination, along with the necessary lifestyle modifications.
... In a study by Shukla et al. about effects of WS on men, WS root powder was used for 3 months and it was shown that sperm parameters such as count and motility in sperm analysis had improved due to decrease apoptosis and reactive oxidative stress among men with normospermia and oligospermia; also copper, zinc, iron, and gold ions of seminal plasma had increased after the treatment and subsequently semen quality increased. This increase in semen quality is proposed to be due to the increase in essential neurotransmitters, metallothionein which has antioxidative function, and metal ions as cofactors for essential enzymes [23]. ...
... This plant has been known to contain more than 80 types of phytochemicals such as steroidal and nonsteroidal alkaloids, steroidal lactones and saponins like isopelletierine, anaferin, anahygrine, hygrine, cuscohygrine, tropine, pseudotropine, withananine, ashwagandha, withaferins, withananinine, pseudowithanine, somnine, somniferine, somniferinine, 3-tropyltigloate, withanine, witha-somine, visamine, mesoanaferine, sitoindoside (7-10), hentriacontane, amino acids such as aspartic acid, glycine, tryptophan, proline, alanine, tyrosine, hydroxyproline valine, cystine, glutamic acid, and cysteine, calcium, phosphorus, iron, flavonoids, starch, reducing sugars, proteolytic enzyme "chamase," glycosides, dulcitol, and volatile oil. Of all these components, withaferin A and sitoindosides had the key role in WS therapeutic effects [11,13,23,33,34,60,61,72]. ...
... Also, the GABA mimetic feature of WS extract is thought to play the main role in inducing gonadotropin releasing hormone secretion and improving hormonal balance [23, 27, 31, 34-36, 42, 44, 47, 51]. In the male reproductive system, it is assumed that WS by providing metal ions facilitates enzyme activities, modifies oxidative stress, and prevents cell apoptosis [23]. The root extract of WS has been shown to induce alanine transaminase activity which increases alanine in seminal fluid leading to a less oxidative stress index and improved semen quality [24]. ...
Introduction
Withania somnifera (WS) also known as ashwagandha is a well-known medicinal plant used in traditional medicine in many countries for infertility treatment. The present study was aimed at systemically reviewing therapeutic effects of WS on the reproductive system.
Methods
This systematic review study was designed in 2016. Required data were obtained from PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, Web of Knowledge, Web of Science, and manual search of articles, grey literature, reference checking, and expert contact.
Results
WS was found to improve reproductive system function by many ways. WS extract decreased infertility among male subjects, due to the enhancement in semen quality which is proposed due to the enhanced enzymatic activity in seminal plasma and decreasing oxidative stress. Also, WS extract improved luteinizing hormone and follicular stimulating hormone balance leading to folliculogenesis and increased gonadal weight, although some animal studies had concluded that WS had reversible spermicidal and infertilizing effects in male subjects.
Conclusion
WS was found to enhance spermatogenesis and sperm related indices in male and sexual behaviors in female. But, according to some available evidences for spermicidal features, further studies should focus on the extract preparation method and also dosage used in their study protocols.
... Withania somnifera also possesses other pharmacological effects. Several studies have shown that it possesses antioxidant activity and inhibits LPO (Shukla et al., 2011) in spermatozoa, which is considered to be a major contributing factor to idiopathic male infertility. In addition, Withania somnifera has been associated with normalization of sex hormone levels in infertile men who are under either psychological, physiological stress, or both, further supporting the adaptogenic qualities of Withania somnifera (Mahdi et al., 2009). ...
... Decreased antioxidant activity occurs when concentrations of antioxidants or functional antioxidative enzymes decrease; dysfunctional enzymes increase; or the amount of ROS increase, which overwhelms the natural antioxidant capacity. As mentioned, the root powder of Withania somnifera (5g/day), when administered daily to infertile men with normozoospermia for 3 months, had decreased ROS production in the seminal plasma and improved sperm count (Shukla et al., 2011). In several studies investigating the effects of Withania somnifera on semen quality in infertile males, enzymatic antioxidant activity was determined by measuring LPO and protein carbonyl groups in seminal plasma, which indirectly depicts the enzymatic activity of SOD and catalase. ...
... In several studies investigating the effects of Withania somnifera on semen quality in infertile males, enzymatic antioxidant activity was determined by measuring LPO and protein carbonyl groups in seminal plasma, which indirectly depicts the enzymatic activity of SOD and catalase. Compared with pretreatment, the amount of LPO was found to decrease after administration of Withania somnifera (Mahdi et al., 2009;Ahmad et al., 2010;Shukla et al., 2011), which is most likely attributed to a synergistic relationship between the increase in the enzymatic activity of SOD and catalase and the innate antioxidant activity of Withania somnifera. Therefore, compounds of the Withania somnifera extract are able to donate electrons and halt the destructive chain reaction of free radicals, thereby lowering the overall ROS burden (Mishra et al., 2000). ...
To manage male infertility caused by hormonal imbalance, infections and other predicaments, multifarious treatment strategies are emerging worldwide. Contemporary treatments, such as assisted reproductive techniques, are costly with low success rates of only 10-30%; however, herbal remedies are gaining more attention as an alternative or supplementary therapeutic modality for male infertility. The beneficial effects induced by oral intake of the roots of a small evergreen shrub, Withania sominifera (Ashwagandha) on semen quality of infertile men have previously been studied. Oral intake of Ashwagandha roots has been found to inhibit lipid peroxidation, improve sperm count and motility, and regulate reproductive hormone levels. The molecular mechanisms of these effects, however, are yet to be unveiled. In this review, we will discuss the role of herbal medicines in male infertility; provide a detailed analysis of various human and animal studies involving Withania somnifera; describe a proposed direct oxidative mechanism involving mitigation of oxidative stress as well as an indirect mechanism consisting of a gamma-aminobutyric acid-like-mimetic pathway ameliorating hormonal balance through crosstalk among different endocrine glands to improve male fertility; and how Withania somnifera supplementation mitigates risk factor-induced male infertility as well as ameliorates male fertility.
... Furthermore, W. somnifera root extract in rats showed significant activity in treating impairment in libido, sexual performance/vigor, penile erectile dysfunction (Ilayperuma et al., 2002;Sahin et al., 2016). Clinical studies of W. somnifera root extract reported activity in psychogenic erectile dysfunction, improving semen and hormone profiles, and oxidative stress in infertile males (Ahmad et al., 2010;Ambiye et al., 2013;Gupta et al., 2013;Mahdi et al., 2011;Mamidi et al., 2014;Shukla et al., 2011). Based on the available scientific literature, this systematic review and meta-analysis aimed to update the efficacy and safety of W. somnifera in infertile men with normozoospermic, oligozoospermic and asthenozoospermic conditions. ...
... The electronic database search resulted in 116 hits and six studies were documented by hand-searching references of relevant studies (Fig. 1). Out of 122 studies, based on the inclusion and exclusion criteria, four clinical trials (comprising 5 publications: observational, n = 4; randomized controlled trial [RCT], n = 1) were included for systematic review (Ahmad et al., 2010;Ambiye et al., 2013;Gupta et al., 2013;Mahdi et al., 2011;Shukla et al., 2011): further results of Ahmad et al., 2010study published in Shukla et al., 2011. The duration of eligible trials was 3 months. ...
... The studies did not show adverse effects with W. somnifera supplementation (Ahmad et al., 2010;Ambiye et al., 2013;Gupta et al., 2013;Mahdi et al., 2011;Shukla et al., 2011). Furthermore, the recent systematic evaluation by Mishra and colleagues also documented W. somnifera with no significant safety concerns (Mishra et al., 2017). ...
Background
: Withania somnifera Dunal, commonly known as Indian ginseng, has been in use since ancient times as anti-stress agent, aphrodisiac, for impotence and infertility treatment.
Purpose
: To evaluate the efficacy and safety of W. somnifera treatment in infertile men.
Study design
: An evidence-based systematic review and meta-analysis using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
Methods
: published literature was searched in PubMed/MEDLINE, EMBASE, Scopus, the Cochrane Library, and DHARA. Grey literature was assessed from the WHO International Clinical Trials Registry Platform (http://apps.who.int/trialsearch/) and the US National Institutes of Health (https://clinicaltrials.gov/).
Results
: Four clinical trials (comprising 5 publications: observational, n = 4; randomized controlled trial [RCT], n = 1) were included in the study. As only one RCT included, meta-analysis of RCT was not performed; however, systematically reviewed data demonstrated statistical (P ≤ 0.002 versus baseline) increase in sperm concentration (167%), semen volume (59%), and sperm motility (57%) in oligospermic males after 90 days of W. somnifera therapy, as well, serum testosterone (17%) and luteinizing hormone (34%) levels. Meta-analysis of observational (versus pre-treatment) studies showed that W. somnifera treatment significantly improved semen parameters (semen volume: mean difference [MD], 0.28 ml; 95% confidence interval [CI], 0.12 to 0.43; P = 0.0004; sperm concentration: MD, 13.57 million/ml; 95% CI, 11.12 to 16.01; P < 0.00001; sperm motility: MD, 8.50%; 95% CI, 7.36 to 9.63; P < 0.00001) with 14% of pregnancy outcome success rate in normozoospermic men. Meta-analysis findings also evidenced significant improvement in serum hormonal profile, oxidative biomarkers and antioxidant vitamins in seminal plasma. No adverse effects were reported in infertile men taking W. somnifera treatment.
Conclusion
: Due to a small number of eligible studies, the available data, though promising, are too limited to provide novel and sufficiently robust evidence of the benefits of W. somnifera in male infertility. Additional RCTs of high quality with a larger sample size are warranted to further strength clinical use of W. somnifera in treating male factor infertility. Future research also needs to elucidate the molecular mechanism(s) of W. somnifera as well its active principles in male infertility.
... To date, six single-nucleotide polymorphisms (SNPs) have been described in the 50 region of the TNF-␣ gene. These polymorphisms modulate IL-6 production and have been associated with susceptibility and severity of a wide range of diseases, including juvenile idiopathic arthritis [11], meningococcal disease and several types of cancers [12], that may be correlation with male fertility. ...
... Positioning of the quadrants on annexin-V/PI dot plots was performed to distinguish between living cells (annexin-V−/PI−), early apoptotic/primary apoptotic cells (annexin-V+/PI−), late apoptotic/secondary apoptotic cells (annexin-V+/PI+) and necrotic cells (annexin-V−/PI+). The FITC and PI fluorescence were measured through a FL-1 filter (530 nm) and FL-2 filter (585 nm), respectively, and 10,000 events were acquired on flow cytometer (Becton-Dickinson, USA) [12]. ...
... One sample from each patient group was selected for the generation of the standard ROS profile for each respective group of subjects (Fig. 1). The generation of ROS was detected by 2,7dichlorfluorescein diacetate (DCFH-DA) [12]. ...
In this study were aimed to identify the association of SNPs candidate genes of TNF-α and IL-6 with hormones levels and sperm cells death in infertile subjects of Uttar Pradesh population in North India. The study population comprised, fertile donor (control group) and infertile group patients i.e. normozoospermic (idiopathic unexplained), oligozoospermic and asthenozoospermic groups, with 260 subjects in each group. Subjects were selected from the Departments of Urology, K.G's Medical University and Urology, SGPGIMS, Lucknow, India. The allele-specific polymerase chain reaction (PCR) and PCR-RFLP were used to investigate the substitution of the guanine (G)-to-adenosine (A) at position-308 and guanine (G)-to-cytosine (C) at position-174 in the promoter regions of the TNF-α and IL-6 genes, respectively. Further their relation to male fertility and sperm function were also investigated. It was found that the substitution levels from G to A and from G to C in the TNF-α and IL-6 genes, respectively, were significantly higher in the infertile subjects as compared to that of control group. The apoptosis and necrosis levels were also higher in oligozoospermic and asthenozoospermic infertile subjects. Further it was found to be associated with increased level of reactive oxygen species as observed in oligozoospermic and asthenozoospermic subjects. However, a significant decrease in testosterone and luteinizing hormone with increased prolactin and follicle stimulating hormones was observed in infertile subjects. The study populations indicating a strong association between TNF-α G-308A and IL-6 G-174C substitution with infertile men which is further supported by allele and genotype meta-analysis and thus established it as a risk factor.
... Our findings are quite similar to those obtained by Skandhan et al. [37], who reported a significant decrease in seminal plasma iron levels in asthenozoospermic and azoospermic patients in comparison to normozoospermic fertile men [37], and suggested that sperm motility disorders may be connected with the decrease in seminal plasma iron concentration. Additionally, a study by Jia et al. [38] reported a positive correlation between Fe levels and sperm concentration and total sperm count, and Shukla et al. [39] showed significantly decreased seminal plasma Fe levels in all infertile groups of patients in comparison to healthy men [39]. On the other hand, Pant and Srivastava [40] did not find significant differences in seminal plasma Fe concentrations between the studied azoospermic, oligoasthenozoospermic, oligozoospermic and asthenozoospermic groups [40]. ...
... Our findings are quite similar to those obtained by Skandhan et al. [37], who reported a significant decrease in seminal plasma iron levels in asthenozoospermic and azoospermic patients in comparison to normozoospermic fertile men [37], and suggested that sperm motility disorders may be connected with the decrease in seminal plasma iron concentration. Additionally, a study by Jia et al. [38] reported a positive correlation between Fe levels and sperm concentration and total sperm count, and Shukla et al. [39] showed significantly decreased seminal plasma Fe levels in all infertile groups of patients in comparison to healthy men [39]. On the other hand, Pant and Srivastava [40] did not find significant differences in seminal plasma Fe concentrations between the studied azoospermic, oligoasthenozoospermic, oligozoospermic and asthenozoospermic groups [40]. ...
Oxidative stress (OS) is one of the reasons for male infertility. Seminal plasma contains a multitude of enzymes and ions which influence OS and thus may affect male fertility. The aim of the study was to check for associations between seminal plasma advanced oxidation protein products (AOPP) concentrations and levels of selected biochemical parameters (total protein, iron, uric acid, magnesium, calcium) in infertile men, and establish whether they are associated with sperm disorders. Seminal plasma AOPP, as well as total protein, iron, uric acid, calcium, and magnesium concentrations, were determined for the following patient groups: normozoospermic (N; n = 33), teratozoospermic (T; n = 30), asthenoteratozoospermic (AT; n = 18), and oligoasthenoteratozoospermic (OAT; n = 28). AOPP concentrations were significantly higher in N and T groups in comparison to AT and OAT groups. Total protein concentrations were significantly lower in the T group in comparison to the AT and OAT groups, whereas iron concentrations significantly decreased in the OAT group in comparison to the T and N patients. AOPP differentiates AT patients from men with other sperm disorders. Our results suggest that asthenozoospermia may be connected with total protein levels. Insufficient iron levels may reflect a decrease in sperm count.
... In a study on infertile men, sperm apoptosis and high concentrations of ROS were observed, that W. somnifera reduced these abnormalities. As a result, W. somnifera can be improved semen quality by reducing cell death and oxidative stress [17]. The extract of this plant (47 mg/100 g) caused testicular development and spermatogenesis in immature rats for 6 days that this was associated with increased LH [18]. ...
... The results of the current research confirmed the results of other studies which showed antioxidants can increase sperm motility [19]. Our results corroborated the findings of other researchers who found alkaloids and flavonoids could increase testosterone level through increasing LH [17]. However, the findings were in contrast with results of other researchers who demonstrated isoflavonid as a stopper of testosterone generation [20]. ...
Purpose: To investigate the comparative effects of Withania coagolans extract and morphine on spermatogenesis in rats Methods: W. coagolans was collected from Sistan and Baluchestan, Iran and 50 and 100 mg/kg body weight doses of methanol extract and 5, 10 and 15 mg/kg body weight doses of morphine were administered parenterally to the rats which were divided into groups. Blood samples were collected and the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were assayed. The testicular tissue was isolated for histopathological examination. Results: No significant changes were observed in levels of LH, FSH and testosterone in treated groups (p < 0.05). However, there was significant difference between the treated groups for extract plus morphine groups, in terms of the number of spermatogonium, spermatocytes and spermatide variation. Moreover, the results indicate tissue disorders in all groups relative to control. The extract caused more disturbances in spermatogenesis compared to morphine, and appears to improve parameters related to spermatogenesis. Conclusion: The results show that the higher dose of Withania coagolans extract (100 mg/kg) exerts varying effects on reproductive parameters. Moreover, the lower dose of Withania coagolans extract (50 mg/kg) enhanced spermatogenesis while also protecting against the damaging effects of morphine. This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest
... During spermatogenesis, mitochondrial activity, and capacitation ROS are produced [69]. In cases of ROS excessive production, such as in obesity or high fat-diet animal models, oxidative damage in polyunsaturated fatty acids via lipid peroxidation (abundant in spermatozoa), nucleic acids (DNA structure) and mitochondrial dysfunction have been described [70,71]. Interestingly, antioxidants might mitigate the deleterious effects of excessive oxidative stress. ...
... Interestingly, antioxidants might mitigate the deleterious effects of excessive oxidative stress. This has been demonstrated in animal studies and in-vitro studies of human sperm [71]. ...
The dramatic increase in the prevalence of obesity coincides with a decline in reproductive health indices in both sexes. Energy excess mediates changes to the regulatory mechanisms of the reproductive system. Obese individuals exhibit increased estrogen concentrations, due to the overexpression of aromatase in the adipose tissue; via a negative feedback loop, men present with symptoms of hypogonadotropic hypogonadism. These hormonal changes, along with increased oxidative stress, lipotoxicity and disturbances in the concentrations of adipokines, directly affect the gonads, peripheral reproductive organs and the embryo. Clinical evidence is somewhat contradicting, with only some studies advocating worse semen parameters, increased incidence of erectile dysfunction, increased doses of ovulation induction medications, and worse live birth rates in assisted reproductive technology (ART) cycles in obese individuals compared with those of normal weight. Similar conclusions are drawn about patients with insulin resistance syndromes, namely polycystic ovary syndrome (PCOS). As far as treatment options are concerned, lifestyle changes, medical therapy and bariatric surgery may improve the reproductive outcome, although the evidence remains inconclusive. In this review, we summarize the evidence on the association of obesity and reproductive health on both the molecular and the clinical level, and the effect of weight-loss interventions on reproductive potential.
... Sperm number, viability, motility and normal morphology of the sperms in the HFD, RHFD, and RHFDA groups were significantly lower than the control group. Interestingly, sperm motility of the RHFDA group was decreased significantly compared to the control group but was significantly higher than HFD and RHFD groups, confirming that ROS may play a role in sperm alteration due to obesity [51].The detrimental effect of ROS on spermatogenesis has been demonstrated also in human spermatozoa, which are known to be susceptible to lipid peroxidation because of their high contents of unsaturated fatty acids [52]. ...
... Impaired spermatogenesis represents another relevant obesity-related andrological complication. Several preclinical studies in animal models have recognized the existence of a negative correlation between obesity and semen quality, probably due to increased seminal oxidative stress, sperm DNA integrity disruption, and increased local release of inflammatory mediators within the reproductive tract [48][49][50][51][52][53][55][56][57]. Moreover, a decrease of pregnancy rate after ART has been demonstrated in obese men [84][85][86]. ...
Obesity is considered a worldwide epidemic disease. Many pathological conditions have been associated to obesity but the evidence relating to impaired fertility in males with obesity are contrasting. The aim of this review was to evaluate the interplay between obesity and male fertility, analyzing evidence from in vitro and in vivo studies to clinical trials. Obesity seems to be responsible of secondary hypogonadism. Here, we propose a new classification including central, peripheral and testicular factors that may affect the hypothalamic-pituitary-gonadal axis. Moreover, some studies demonstrated a direct action of obesity on sperm count and sperm characteristics, mediated by impaired Sertoli cells function, increased scrotal temperature, oxidative stress and accumulation of toxic substances and liposoluble endocrine disruptors in fat tissue. Recent studies have explored obesity-related epigenetic effects in sperm cells which may cause diseases in offspring. Moreover, not only in females but also males, obesity has been linked to reduced outcomes of in vitro fertilization, with a reduction of pregnancy rate and an increase of pregnancy loss. Finally, we reviewed the effects of weight modifications through diet or bariatric surgery on obesity-related reproductive dysfunction. In this regard, several studies have demonstrated that weight loss has been associated with a restoration of gonadal hormones levels.
... In the WS group, patients received a daily dose of six capsules designed in two different colours (containing 5 g of WS root) Shukla et al., 2011) in three divided doses; in the pentoxifylline group, subjects received six capsules in two different colours (containing 800 mg of this drug and a placebo) (Mehni, Ketabchi, & Hosseini, 2014) three times a day over 90 days. Every meal of the patient must have included capsules from both colours. ...
... WS root also enhances alanine transaminase activity, which leads to an increase in the semen alanine content. Alanine then protects spermatozoa against oxidative stress-induced damage and increases sperm count and motility (Gupta et al., 2013;Shukla et al., 2011). Steroidal lactones and withanolide contents of WS including sitoindosides VII-X and withaferin-A appear to be responsible for the therapeutic ef- However, we also found that the chronic and regular use of pentoxifylline improves sperm parameters in infertile male patients. ...
... 2002; Singh et al. 2002;Chaudhary et al. 2003;Naidu et al. 2003). These effects have been attributed to protect against oxidative stress (a common causative factor for these disorders) (Jain et al. 2001;Ahmad et al. 2010;Parihar et al. 2004;Shukla et al. 2011a) and often lead to physiological and behavioral rejuvenation (Kumar et al. 2005;Naidu et al. 2006;Sankar et al. 2007;Bhattacharya et al. 2001) (Fig. 14.1). Cell culture studies have exhibited that such effect is modulated by NRF2, a key antioxidant protein (Reuland et al. 2013). ...
... Cell culture studies have exhibited that such effect is modulated by NRF2, a key antioxidant protein (Reuland et al. 2013). Several experimental oxidative stress models in rodents including exposure to streptozotocin, maneb, paraquat, bromobenzene, nicotinamide streptozotocin and rotenone have endorsed antioxidant and neuroprotective activity of Ashwagandha extracts (Ahmed et al. 2013;Prakash et al. 2013;Vedi et al. 2014;Manjunath and Muralidhara 2013;Shukla et al. 2011aShukla et al. , 2012Anwer et al. 2012). The effects have been assigned to active constituents including withanolide A (Soman et al. 2012) and glyco-withanolides (Bhattacharya and Muruganandam 2003). ...
Rapidly growing population, social and environmental factors are continuously exerting impact on social and psychological human health in multiple ways. In particular, these factors cause cumulative stress affecting cognitive functions and elevate risks of diverse neuronal dysfunction and malignant brain diseases. Maintenance of brain health has hence emerged as a new challenge in increasing old age populations worldwide. Use of herbal drug constituents has emerged as a preferred choice due to enormous undesirable side effects of pharmacological drugs. Ashwagandha, a sub-tropical medicinal plant has been extensively used in Indian traditional home medicine system i.e. called “Ayurveda” for its stress-, hypertension-, aging-, neurological dysfunction- and malignant growth-inhibitory properties. Detailed molecular insights of these activities and mechanism(s) are only beginning to be demonstrated by laboratory studies. In this chapter, we attempt to sketch research evidence of the benefits of Ashwagandha bioactives for brain health.
... Additionally, it exhibits free radical scavenging and antioxidant properties [213]. Several studies have reported the beneficial effects of W. somnifera in the treatment of male infertility, including an improvement in sperm count [214], concentration, motility [214][215][216], seminal plasma antioxidant status [214,216] and decreased lipid peroxidation [226,228], sperm ROS production and apoptosis [217] in infertile patients [214,215,217] and in normozoospermic infertile patients [216]. Furthermore, a study with streptozotocin-induced diabetic rats has also shown that a W. somnifera root extract decreases lipid peroxidation and ROS production in the cytosol and mitochondria of testicular cells, and restores antioxidant system defenses [218]. ...
... Additionally, it exhibits free radical scavenging and antioxidant properties [213]. Several studies have reported the beneficial effects of W. somnifera in the treatment of male infertility, including an improvement in sperm count [214], concentration, motility [214][215][216], seminal plasma antioxidant status [214,216] and decreased lipid peroxidation [226,228], sperm ROS production and apoptosis [217] in infertile patients [214,215,217] and in normozoospermic infertile patients [216]. Furthermore, a study with streptozotocin-induced diabetic rats has also shown that a W. somnifera root extract decreases lipid peroxidation and ROS production in the cytosol and mitochondria of testicular cells, and restores antioxidant system defenses [218]. ...
During the last decade, several studies have shown that mitochondrial parameters, such as integrity, respiratory activity, membrane potential and ROS production are intimately linked with sperm quality. Given the limitations of conventional semen analyses in terms of predicting male fertility, an increasing number of studies are focusing on the characterization of sperm mitochondria in order to more accurately assess sperm functionality. Moreover, mitochondria from several organs, such as the liver, have been described as a powerful screening tool for drug safety, being an easy in vitro model to assess the toxicity of distinct families of compounds. Given that mitochondrial functionality is intimately related to sperm homeostasis, it has become important to understand how compounds, ranging from dietary supplements, environmental pollutants, dependency-inducing drugs to pharmacological agents (such as erectile dysfunction-targeted drugs and male contraceptives) affect sperm mitochondrial function. In this review we discuss studies describing the effects of various chemical agents on spermatozoa, with particular emphasis on mitochondrial function. From the extensive literature analyzed we conclude that in some cases the role of sperm mitochondria as putative predictors of sperm functionality is very obvious, while in others further studies are needed to clarify this issue.
... The results proved the protective effect of W. somnifera as illustrated by the previous studies, since proved the regulation effect of the W. somnifera due to antioxidant [35] and anti-inflammatory properties which Nasimi et al., 2018 [36] found that W. somnifera enhances spermatogenesis in male and sexual behaviors in female; in addition, mechanism of W. somnifera perspicuous effect on the reproductive system is antioxidative features and its ability to improve the hormonal balance of LH and FSH and improve detoxification process [37], which plays a main role in inducing gonadotropin releasing hormone secretion [35]. The previous study illustrated the positive effect of W. somnifera on histological on different tissue [38], as other extract on the testis tissue testicular and ovary [39]. ...
Morphine is one of the most types of phenanthrene alkaloid opioid used to soothe the acute and chronic pain via narcotic and analgesic medical employment. Increasingly constantly used of opioid in the public and medication practical important knowledge improve that. Morphine show pernicious has effects on numerous tissue for instance ovary, liver and lung morphine side effects instruct for existence of oxidative role due to generation of reactive oxygen species in the affected tissue. Last decades researchers proved that natural substance provides protective role against toxic effect. Thus, withania somnifera consider as antioxidant substance provide protective versus the toxic substance as morphine. The present study wase aimed to evaluate the protective role of withania somnifera extract on the level of sex hormone in morphine addicted female rats. In conclusion, the present study confirmed a truth evidence of a protective roles of withania somnifera against the morphine addiction in female rats.
... The roots of W. somnifera are often used as an aphrodisiac [47]. Multiple studies have demonstrated that it has antioxidant properties and suppresses lipid peroxidation in sperm cells [48], which is thought to be a major contributor to idiopathic male infertility. Furthermore, W. somnifera has indeed been linked to the restoration of sex hormones in infertile men who are under mental, physiologic, or even both types of stress, indicating that it possesses adaptogenic properties [49]. ...
Male infertility is responsible for an estimated 50% of all cases of infertility. Treatments for male infertility include surgery, in-vitro fertilization, hormone therapy, and herbal remedies. Assisted reproductive technologies and methods have made it possible to identify and treat previously untreatable causes of male infertility. Currently available treatments for male infertility are prohibitively expensive, difficult to obtain, necessitate a lengthy course of treatment, and have a host of side effects. Herbal therapy offers male infertility treatment that is less expensive and has fewer side effects than other treatments. The current review focuses on the various treatment options for male infertility.
... Among these chemical ingredients, sitoindosides and withaferin A had the leading role in WS therapeutic effects. [10][11][12][13][14] Ashwagandha has the potential to treat joint inflammation, nervous system disorders, diabetes, hyperlipidemia, attention deficit hyperactivity disorder, hiccup, obsessive-compulsive disorder, bronchitis, back pain, sleep deprivation, tumors, Parkinson's disease, tuberculosis, menstrual irregularities, and chronic liver disease. 15 Ashwagandha roots possess antioxidant properties and treat infertility, the immune system and cardiovascular disease. ...
... Among these chemical ingredients, sitoindosides and withaferin A had the leading role in WS therapeutic effects. [10][11][12][13][14] Ashwagandha has the potential to treat joint inflammation, nervous system disorders, diabetes, hyperlipidemia, attention deficit hyperactivity disorder, hiccup, obsessive-compulsive disorder, bronchitis, back pain, sleep deprivation, tumors, Parkinson's disease, tuberculosis, menstrual irregularities, and chronic liver disease. 15 Ashwagandha roots possess antioxidant properties and treat infertility, the immune system and cardiovascular disease. ...
Background: Phytomedicine is becoming more acceptable as an alternative medicinal approach in the modern era.
Objectives: The current study examined the antioxidant capacity and in vitro response of phytochemical constituents of Withania somnifera (Ashwagandha) on standard parameters of healthy volunteer semen.
Methods: The phytochemicals and their pharmacological response in a hydroethanolic (30:70 v/v) extract of W. somnifera roots were determined using standard protocols.
Results: The constituents included flavonoids, phenolic acids, alkaloids, and terpenoids were reported. High-performance liquid chromatography and Fourier-transform infrared spectroscopy determined a diverse array of biologically active chemical constituents in the extract. The extract of W. somnifera exhibits substantial antioxidant properties, including total antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl inhibition, H 2 O 2 scavenging, and Fe ³⁺ reducing potential ( P < .05). The analysis of essential natural minerals explored adequate levels determined using atomic absorption spectrophotometer. Cytotoxic studies revealed significant thrombolytic, RBC membrane stabilization, and DNA damage protection activity ( P < .05) while remaining non-mutagenic against Salmonella typhi TA98 and TA100. The best protective response of W. somnifera extract on human semen parameters (n = 30), such as total motility, progressive motility, and viability, demonstrated a significant ( P < .05) improvement, particularly at the dose of 25 μg/mL and 50 μg/mL.
Conclusion: The study concludes that W. somnifera possesses favorable in vitro characteristics that could aid in the preservation of sperm during intrauterine insemination and in vitro fertilization.
... In addition, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Third, ROS excessive production is known to have negative effects on male fertility [30,32,33]. Another noteworthy reason is the increased scrotal temperature. ...
The meta-analysis aimed to explore the possible relationship between bariatric surgery and semen quality. PubMed, EMBASE, and CENTRAL were searched from database inception through October 28, 2021. Articles were eligible for inclusion if they evaluated the impact pre- and post-bariatric surgery on semen parameters. A total of 9 studies with 218 patients were found. The mean preoperative age distribution of the patients included centralized from 18 to 50 years, and the mean pre-op BMI ranged from 36.7 to 70.5 kg/m². The follow-up period ranged from 6 to 24 months. The results revealed that bariatric surgery had no significant effect on sperm volume, concentration, total count, morphology, total motility, progressive motility, viability, semen pH, and semen leukocytes. Bariatric surgery does not improve semen quality in obese males.
... It reduced oxidative stress, inhibited lipid peroxidation with an increase in antioxidants [10]. A study by Shukla et al. [334] showed a reduction of ROS and apoptosis along with an increase in essential metal ions (Cu 2+ , Zn 2+ , Fe 2+ , and Au 2+ ) in seminal plasma resulted in improved semen quality. High-concentration full-spectrum extract of WS root (300 mg capsule for 60 days) significantly reduced serum cortisol and provided resistance towards stress in a double-blind, randomized, placebo-controlled trial [68]. ...
Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.
... More studies with larger sample size and placebo control group Shukla et al. (2011) 4.Effect of Ws root extract on spermatogenic activity 46 male patients with oligospermia were included and randomized to treatment with extract ( = 21) or placebo ( = 25) on the same protocol. ...
... Withania somnifera is a medicinal plant with free radical scavenging and antioxidant properties (Umadevi, 1996, Misra et al., 2000, and several in vivo studies in humans have reported many reproductive health benefits of W. somnifera treatment in male infertility, including an improvement in sperm count , concentration and motility Ambiye et al., 2013), seminal plasma antioxidant status Mahdi et al., 2011), decreased lipid peroxidation Mahdi et al., 2011), increased sperm ROS production, and decreased apoptosis in infertile patients Shukla et al., 2011;Ambiye et al., 2013) and in normozoospermic infertile patients (patients with normal semen parameters; Mahdi et al., 2011). Furthermore, the W. somnifera root extract (oral gavage, 500 mg/kg/15 days) decreases lipid peroxidation and ROS production in the cytosol and mitochondria of testicular cells and restores antioxidant defenses in streptozotocin (single i.p.; 90 mg/kg)-induced diabetic rats (Kyathanahalli et al., 2014). ...
This chapter focuses on the possible effects of different classes of chemical compounds on sperm mitochondria as a surrogate for fertilization potential. Oral carnitine supplementation improved sperm morphology and consequently sperm quality, suggesting a beneficial role on sperm mitochondria, through either antioxidant or metabolic properties. Endocrine-disrupting chemicals (EDCs), commonly known as endocrine disruptors, are exogenous substances that interfere with hormonal homeostasis, mimicking endogenous hormones and affecting their production, binding, and/or action. Studies have focused on the negative effects of drugs linked to substance abuse or on environmental toxicants, especially those with hormonedisrupting effects. There are several isomers of vitamin E, a lipid-soluble molecule not synthesized in mammalian cells, such as tocopherols and tocotrienols, with alpha-tocopherol being the most active form. The medicinal properties of several plants and plant products have been recognized for many years, mainly owing to the knowledge from indigenous tribes.
... Male infertility is globally increasing and accounts for approximately 50% of infertile couples [1]. There are a number of factors responsible for male infertility, including excessive synthesis of reactive oxygen species (ROS). ...
A thiol group plays an essential role in sperm metabolism and the antioxidative defense state. Zinc is the second most abundant element in the human body, following iron. The present study was conducted to study the effect of zinc supplementation on the characteristics of semen along with thiol and thiol-related enzymes in semen of asthenospermic patients. Semen samples were obtained from 60 fertile and 60 asthenospermic men, from couples who had consulted the infertility clinic of Babil Hospital (Hillah city, Iraq). The subfertile group was treated with zinc; every participant took two 220 mg capsules of zinc sulfate per day for 3 months. Semen samples were obtained (before and after zinc supplementation). The levels of reduced thiol, oxidized thiol, thiol oxido-reductive index, and thiol-related enzymes activities were determined in spermatozoa and seminal plasma of patients and healthy groups. Oxidized thiol levels were significantly higher in the infertile patients compared to that in the fertile group. Conversely, reduced thiol level, sulfhydryl oxidase activity, and glutathione peroxidase activity significantly decreased in the infertile patients compared to that in the fertile group. Oxidized thiol levels, reduced thiol levels, and thiol-related enzymes activities of the infertile patients were restored to normal values after treatment with zinc. However, reduced and oxidized thiol levels in spermatozoa did not change significantly in the group treated with zinc. The quantitative values for RSH/RSSR and thiol-related enzymes may provide useful means to qualitatively express the oxidant/antioxidant balance in clinical and epidemiologic studies. ClinicalTrials.gov Identifier: NCT02985905.
... Consequently, oxidative stress contributes to majority of brain dysfunctions including memory impairment (Mattson 2004). Aging and neurodegenerative diseases such as Parkinson's, Alzheimer and Huntington's associated memory decline results largely from oxidative damage (Di Carlo et al. 2012;Shukla et al. 2011). Ashwagandha extracts exhibit enormous potential of scavenging free radicals and activating antioxidant signalling pathways in various chemically induced and physiological models of memory loss both in vitro and in vivo. ...
The search for therapeutic candidates of memory disorders including gene targets and compounds both synthetic and natural has been a prime arena of neurobiology research. Amongst suggested therapeutic compounds, several herbal products with a long history of use in Ayurveda have gained attention in modern medicine. Ashwagandha (Withania somnifera) also referred to as “Queen of Ayurveda” is at the zenith of Ayurvedic herbs owing to its tremendous potential to recover memory decline in aging and neurodegenerative pathologies as well as enhance basal memory function of healthy individuals. Despite such promising effects, limited mechanistic evidences have hindered its acceptance in modern medicine. However, technical advances in neuroscience research over the past decade have filled-in some gaps in understanding of molecular and mechanistic biology of Ashwagandha effects. In this chapter, we highlight the studies that have deciphered the cellular and molecular mechanisms of memory enhancing potential of Ashwagandha in various disease models. Cellular targets of Ashwagandha include (i) activation of antioxidant defence system rescuing nerve cells from apoptosis, oxidative stress and DNA damage, (ii) induction of cholinergic system and (iii) up-regulation of memory linked neuroplasticity genes and neuronal arborisation. All of these molecular effects translate into increase in memory. Such multiple-module action has intrigued research to unravel upstream master regulators of Ashwagandha effects on gene expression, cell physiology and behaviour.
... Similarly, the seminal plasma levels of the essential metal ions Cu 2+ , Zn 2+ , Fe 2+ and Au 2+ were low. Treatment with Withania somnifera significantly reduced the sperm apoptosis, ROS levels and improved serum metal ion levels of infertile men of all the age groups under study (Shukla et al. 2011). 3. ...
Withania somnifera is wonder shrub used traditionally as a folk medicine for several remedies in the Indian subcontinent. During last few decades numerous scientific studies have shown the potential therapeutic prospects of this herb and of its various constituents in different disease models. Several classes of compounds including withanolides, sitoindosides and other useful alkaloids have been isolated from this plant with promising medicinal value. It has been demonstrated that different parts of plant including roots, leaves and fruits exhibit unique biological activities that actually are manifested to the presence and the abundance of specific constituent/s in the respective parts of the plant. It was also established that same plant grown at different locations under varied environmental conditions influences the synthesis of the individual constituents in different parts of the plant, hence their biological activities. Studies conducted in cellular and murine models have shown that extracts made of roots bear immune activating properties, whereas leaf extracts showed anticancer activities. It has been observed that root and leaf extracts of plant characterised with about a dozen markers displayed that root extracts demonstrated Th1 specific immunomodulatory and anti-inflamatory activities, whereas leaf extracts showed anticancer properties, respectively. It was further explored that anti-cancer potential of leaf extracts was mainly due to Withaferin A, a potent cytotoxic withanoloid, existing in abundance and a major constituent in the leaves of the plant. Similarly, anti-inflammatory and Th1 immune skewing properties of the root extract was conferred to the higher amount of Withanolide A, present in the roots of the plant along with other constituents. Meanwhile several studies have deciphered the role of individual constituents in various biological activities with extensive mechanism of action discussed in this review. This review while summarises the potential medicinal benefits of the W.somnifera, it also emphasizes that marketed product of the plant extracts for human consumption should scientifically validated for bioactive constitutents.
... Mahdi et al. 2011 also defined the role of stress in male infertility after measuring various biochemical and stress parameters before and after treatment. Study reported that root powder at the dose of 5 g/day for 3 months treat stress-related infertility improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals Shukla et al. 2011). Kumar et al. (2015b) revealed that W. somnifera also reversed the effect of sodium arsenite administration on sperm counts and sperm motility and also maintains the cellular integrity of testicular cells leading to normal functioning of it. ...
Withania somnifera Dunal, is a commonly used herb in Indian Ayurvedic medicine system. Due to its pharmacological value and an inexhaustible source of novel biologically active compounds, it has been a great interest for researchers. The plant is known to possess anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory and hemopoetic properties. Various withanolides, steroidal lactones, have been isolated from W. somnifera and were known to have high therapeutic value. Based on the differences in the substitution patterns of withanolides the species has been classified into various chemotypes. So far, three different chemotypes have been identified, which have been further classified into ecotypes based on the contents of withanolides. Present review summarizes the phytochemical variability and pharmacological advances reported in literature.
... Withania somnifera (ashwagandha) is an Ayurvedic herb which has traditionally been used for its stress-reducing and aphrodisiac qualities. There is some evidence that W. somnifera can improve semen quality by reducing oxidative stress, 24,25 and increase levels of testosterone. 24 A small RCT of men with oligospermia were randomized to either Ayurvedic treatment with W. somnifera or a placebo for 90 days. ...
Complementary therapies and medicines are a broad and diverse range of treatments, and are frequently used by women and their partners during the preconception period to assist with infertility, and to address pregnancy-related conditions. Despite frequent use, the evidence examining the efficacy, effectiveness, and safety for many modalities is lacking, with variable study quality. In this article, we provide an overview of research evidence with the aim of examining the evidence to inform clinical practice. During the preconception period, there is mixed evidence for acupuncture to improve ovulation, or increase pregnancy rates. Acupuncture may improve sperm quality, but there is insufficient evidence to determine whether this results in improved pregnancy and live birth rates. Acupuncture can be described as a low-risk intervention. Chinese and Western herbal medicines may increase pregnancy rates; however, study quality is low. The evaluation of efficacy, effectiveness, and safety during the first trimester of pregnancy has most commonly reported on herbs, supplements, and practices such as acupuncture. There is high-quality evidence reporting the benefits of herbal medicines and acupuncture to treat nausea in pregnancy. The benefit from ginger to manage symptoms of nausea in early pregnancy is incorporated in national clinical guidelines, and vitamin B6 is recommended as a first-line treatment for nausea and vomiting in pregnancy. The safety of ginger and vitamin B6 is considered to be well established, and is based on epidemiological studies. Acupuncture has been shown to reduce back pain and improve function for women in early pregnancy. There is little evidence to support the use of cranberries in pregnancy for prevention of urinary tract infections, and chiropractic treatment for back pain. Overall the numbers of studies are small and of low quality, although the modalities appear to be low risk of harm.
... 18 Ashwagandha also inhibited lipid peroxidation and improved sperm count and motility, antioxidant levels, serum testosterone and luteinizing hormone (LH) and reduced levels of follicular stimulating hormone (FSH) and prolactin, 19 helps in proliferation of spermatogenic cells, improves semen quality by reducing oxidative stress and cell death, as well as improving essential metal ion concentrations. 20 It also repairs the disturbed concentrations of lactate, alanine, citrate, GPC, histidine and phenylalanine in seminal plasma and recovers the quality of semen of post-treated compared to pretreated infertile men. 21 Mucuna pruriens (Kapikachchhu) seeds are rich source of L-DOPA and its metabolites which stimulate the hypothalamus and forebrain to secrete gonadotropin releasing hormone (GnRH) 22 which in turn, upregulates the anterior pituitary gland to secrete FSH and LH causing increased synthesis of testosterone by leydig cells of the testis. ...
Enhanced rate of divorce among most elite couple in metros alarmed a unique social stigma. A man who is full of stresses of life and lost his manhood is accepting his failure and ready to sign paper of divorce in court as an escape route to get rid of his responsibility. Erectile dysfunction (Klaibya) or impotence is emerging as one of the most serious life style and stress related disease. Over exertion, physiological disturbances, lowered level of hormones and strained relationship with partner are the main causes for this disease. The remedial measure of Erectile dysfunction (ED) is still evolving in conventional system of medicine. The search for a perfect aphrodisiac drug specially a herbo-mineral drug that will heighten sexual desire, pleasure and performance has been a continuing cultural quest from ancient era to current times. Therefore, a herbomineral formulation was prepared, which consists of Vanga Bhasma, Ashwagandha (Withania somnifera) Churna and Kapikachhu (Mucuna pruriens) Churna with three Bhavana of each Dhatura (Datura metel) Patra Swarasa and Bhanga (Cannabis sativa) Kwatha to evaluate the clinical effect in 40 male diagnosed patients of Klaibya (Erectile dysfunction). Out of 40 patients Klaibya of 29 completed the full course of trial treatment and 11 patients were dropped out from the study. The result of 29 patients showed statistically significant improvement in some sexual symptoms and seminal parameters.
... Oxidative stress -Oxidative stress has been closely connected to neurodegenerative disorders (Di Carlo et al., 2012;Shukla et al., 2011). Molecular mechanisms of glutamate-induced neurotoxicity and excitotoxicity, although have not been completely understood, these are often interlinked with oxidative stress. ...
Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory.
... W. somnifera, also counteract the oxidative damage to the sperm and reactive oxygen species associated with abnormal sperm parameters leading to infertility (Ambiye et al., 2013). In recent years, it has been well documented that W. somnifera improves semen quality by effectively reducing oxidative stress and improving reproductive hormone levels in infertile male patients (Ahmad et al., 2010;Shukla et al., 2011). In clinical trials with infertile male patients, W. somnifera repairs the altered concentrations of lactate, alanine, citrate, glycerylphosphorylcholine, histidine, and phenylalanine in seminal plasma, and it recovers the quality of semen of post-treated compared to pre-treated men, in addition to inducing spermatogenesis in infertile male patients (Ambiye et al., 2013;Gupta et al., 2013). ...
Withania somnifera (Ashwagandha) is an important Rasayana herb and widely considered as Indian ginseng in Ayurveda. In traditional system of Indian medicine, it is used as tonic to rejuvenate the body and increase longevity. In Ayurvedic preparations, various parts of the plant have been used to treat variety of ailments that affect the human health. However, dried roots of the plant are widely used for the treatment of nervous and sexual disorders. The major active chemical constituents of this plant are withanolides, which is responsible for its wide range of biological activities. Since the beginning of the 20 th century, a significant amount of research has been done and efforts are ongoing to further explore other bioactive constituents, and many pharmacological studies have been carried out to describe their disease preventing mechanisms. In this chapter, we have reviewed the chemistry and pharmacological basis of W. somnifera in various human ailments.
... However, little is known about the reversal of stress conditions and semen quality improvement. Two papers were found in which stress was successfully treated with Conveyer of Modulating Radiance therapy [15] or with plant therapy (Withania somnifera) [16] . Semen quality improved in both. ...
Objective: It was the aim of this research to assess whether Tadalafil 5 mg once daily can improves the sperm count of unexplained infertile males with erectile deficiency induced by the emotional stress of attempting to father children. Methods: Two groups, each made up of 30 unexplained infertile males with psychogenic erectile deficiency related to attempts to father children received Tadalafil 5 mg once daily (Group 1) or a placebo (Group 2) for one month. Unexplained infertile men are intended as normospermic men who could not father children over a one year period and whose female partner is free of factors causing infertility. The endpoints were: differences between the groups in restoring erectile response, modifying sperm count, side effects and modifications of sperm analyses with respect to resolution or not of the erectile deficiency irrespective of the substance (Tadalafil or placebo) used. The means were compared using analysis of variance and the percentages using the chi square test. Results: The patients who received Tadalafil had their sperm volume, concentration and motility increased, but not the percentage of typical forms. Patients who received a placebo had no significant improvement. Additional analyses indicated that sperm volume, concentration and motility (but not morphology) significantly increased only in the patients who restored erectile response to sexual stimulation, independently of Tadalafil or placebo administration. No significant side effects were present. Conclusions: It is thought that therapies aimed at removing emotional stress linked to the performance anxiety of fathering children might improve sperm count in unexplained infertile couples.
... Human spermatozoa are known to be susceptible to lipid peroxidation because of their high contents of unsaturated fatty acids (Shukla et al., 2009). ROS is produced normally in cellular metabolism and its low concentration is essential with biopositive effect on normal functioning of the sperm cell as it enhances spermatozoa ability to bind with zona pellucida, whereas in excess, can attack nuclear and mitochondrial DNA, inducing fragmentation, aberrant recombination and/or defective packaging (Shukla et al., 2011). Hence, oxidative stress induced by excess amount of ROS may lead to changes in the tertiary structure and expression of proteins, protein membrane receptors, and membrane transport proteins, eventually resulting in disturbed ionic balance Chambial et al., 2013). ...
The aim of this review was to provide current scenario linking obesity and male fertility. Obesity has been linked to male fertility because of lifestyle changes, internal hormonal environment alterations, and sperm genetic factors. A few studies assessing the impact of obesity on sperm genetic factor have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm genetic factor and obesity. There are emerging facts that obesity negatively affects male reproductive potential not only by reducing sperm quality, but in particular it alters the physical and molecular structure of germ cells in the testes and ultimately affects the maturity and function of sperm cells. Inhibition of microRNA in the male pronucleus of fertilized zygotes produces offspring of phenotypes of variable severity depending on miRNAs ratios. Hence, these RNAs have a role in the oocyte development during fertilization and in embryo development, fetal survival, and offspring phenotype. It has been reported that the miRNA profile is altered in spermatozoa of obese males, however, the impact of these changes in fertilization and embryo health remains as yet not known.
Male infertility is linked to several environmental and mutagenic factors. Most of these factors, i.e., lifestyle, radiations, and chemical contaminations, work on the fundamental principles of physics, chemistry, and biology. Principally, it may induce oxidative stress (OS) and produce free radicals within the cells. The negative effect of OS may enhance the reactive oxygen species (ROS) levels in male reproductive organs and impair basic functions in a couple’s fertility. Evidence suggests that infertile men have significantly increased ROS levels and a reduced antioxidant capacity compared with fertile men. Although, basic spermatic function and fertilizing capacity depend on a delicate balance between physiological activity of ROS and antioxidants to protect from cellular oxidative injury in sperm, that is essential to achieve pregnancy. The ideal oxidation-reduction (REDOX) equilibrium requires a maintenance of a range of ROS concentrations and modulation of antioxidants. For this reason, the chapter focuses on the effects of ROS in sperm functions and the current concepts regarding the benefits of medical management in men with diminished fertility and amelioration of the effect to improve sperm function. Also, this evidence-based study suggests an increasing rate of infertility that poses a global challenge for human health, urging the need of health care professionals to offer a correct diagnosis, comprehension of the process, and an individualized management of the patients.KeywordsMale fertilityFertility impairmentSperm functionFree radicalsOxidative injury
Some of the areas of concern in andrology are erectile dysfunction, late onset hypogonadism, benign prostatic hyperplasia, and infertility. Often these are associated with depletion in androgens, particularly the testosterone hormone. Lack of physical, mental, and sexual vitality, particularly in elderly men, is recognized as a worldwide health problem, which is challenging medically as well as in healthcare. There are numerous traditional herbal products that claim to enhance male overall well-being and restore reproductive health. Proof of acceptance and relevance of herbal treatment in men’s health management are underlined by the tremendous number of publications as well as clinical data, which meet the highest quality, safety, and efficacy standards. This chapter reviews scientific evidence from clinical trials performed with well-known traditional herbs, claiming therapeutic benefits in men’s health: Eurycoma longifolia (tongkat ali), Lepidium meyenii (maca), Withania somnifera (ashwagandha), and Trigonella foenum-graecum (fenugreek). Furthermore, information of acceptance in terms of regulatory issues is summarized.
Several medicinal plants are traditionally used in different regions of Africa for the treatment of male infertility, sexual asthenia, erectile dysfunction, and impotency or used as an aphrodisiac. Scientific studies, mostly conducted in vitro or in animals, have proven the acclaimed traditional use of these plants to enhance sexual activities or sperm concentration, motility, and viability. Some of the mechanisms of actions associated with these plants include increased level of testosterone and the relaxation of the smooth cavernosal muscles. However, some plants were also shown to have detrimental effects on the male reproductive system. This may be due to the varying modes of plant extraction, duration of treatment, experimental design, dosage used, quality of the plant, or toxic effects. There is a need to standardize the protocols as well as to better understand the mechanism of actions of the respective plants. Further studies should be conducted using human subjects.
Withania somnifera L. is a multipurpose medicinal plant of family Solanaceae occurring abundantly in sub-tropical regions of the world. The folk healers used the plant to treat several diseases such as fever, cancer, asthma, diabetes, ulcer, hepatitis, eyesores, arthritis, heart problems, and hemorrhoids. The plant is famous for the anti-cancerous activity, low back pain treatment, and muscle strengthening, which may be attributed to the withanolide alkaloids. W. somnifera is also rich in numerous valued secondary metabolites such as steroids, alkaloids, flavonoids, phenolics, saponins, and glycosides. A wide range of preclinical trials such as cardioprotective, anticancer, antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, anti-depressant, and hypoglycemic have been attributed to various parts of the plant. Different parts of the plant have also been evaluated for the clinical trials such as male infertility, obsessive-compulsive disorder, antianxiety, bone and muscle strengthening potential, hypolipidemic, and antidiabetic. This review focuses on folk medicinal uses, phytochemistry, pharmacological, and nutrapharmaceutical potential of the versatile plant.
Withania somnifera (L.) Dunal, commonly known as Ashwagandha, is a high value medicinal plant of the family Solanaceae. Besides the drier parts of India, it also grows up to a hight of 1,700 meters in Himalayan region (mainly Himachal Pradesh, Uttarakhand and Jammu & Kashmir). It possesses a wide array of health benefits due to the presence of several bio-active metabolites in it, mainly belonging to a class called as Withanolides (a group of steroidal lactones with a basic C-28 framework) and have been repeatedly found effective against some of the important human ailments. With the growing market of herbal drugs and increase in the market demand of Ashwagandha, the major challenges in this crop (low seed viability, losses due to pest/diseases, quality maintenance of herbal products etc.) need to be addressed in a systematic manner. Several efforts have been made to explore the variability (morphological, genetic and chemotypic) in its germplasm and also to identify the key genes of the withanolide biosynthetic pathway. Many attempts have also been made to increase the production of bio-actives in W. somnifera both under in vivo and in vitro conditions. Keeping this in mind, the present book chapter have been structured to discuss the major challenges and major crop improvement/breeding objectives in this crop. Further, we have tried to highlight the OMICS (proteomic, transcriptomic, genomic and metabolomic) studies made in this plant which, will may help in designing suitable strategies for the improvement of this medicinal plant crop. Various biotechnological intervention (tissue culture, genetic transformation etc.) tried in this crop for its improvement have also been discussed, which will provide a holistic view of the crop improvement efforts made in this important medicinal plant species.
It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants
could have a significant role in the treatment of male infertility. The main objectives of this study are: 1) to systematically review
the current evidence for the utility of antioxidants in the treatment of male infertility; and 2) propose evidence-based clinical
guidelines for the use of antioxidants in the treatment of male infertility. A systematic review of the available clinical evidence was
performed, with articles published on Scopus being manually screened. Data extracted included the type of antioxidant used,
the clinical conditions under investigation, the evaluation of semen parameters and reproductive outcomes. The adherence to the
Cambridge Quality Checklist, Cochrane Risk of Bias for randomized controlled trials (RCTs), CONSORT guidelines and JADAD
score were analyzed for each included study. Further, we provided a Strength Weakness Opportunity Threat (SWOT) analysis to
analyze the current and future value of antioxidants in male infertility. Of the 1,978 articles identified, 97 articles were included
in the study. Of these, 52 (53.6%) were uncontrolled (open label), 12 (12.4%) unblinded RCTs, and 33 (34.0%) blinded RCTs,
whereas 44 (45.4%) articles tested individual antioxidants, 31 (32.0%) a combination of several products in variable dosages, and
22 (22.6%) registered antioxidant products. Based on the published evidence, we 1) critically examined the necessity of additional
double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for antioxidant
therapy in male infertility. The current systematic review on antioxidants and male infertility clearly shows that antioxidant
supplementation improves semen parameters. In addition, it provides the indications for antioxidant treatment in specific clinical
conditions, including varicocele, unexplained and idiopathic male infertility, as well as in cases of altered semen quality.
Withania somnifera is a very unique medicinal plant explored by number of orthodox medicinal systems such as Ayurveda, Siddha and Unani. It is commonly known as Ashwagandha, Indian ginseng and winter cherry, and finds its potential medicinal properties in the Ayurvedic Pharmacopoeia of India and Siddha Pharmacopoeia of India. The Withania genus is classified under the Solanaceae family and includes around 60 species, among which W. somnifera and W. coagulans are often mentioned in Ayurveda. Ashwagandha is a treasure house of widespread array of metabolites such as steroids, flavones, alkaloids, carbohydrates, glycosides, saponins, tannins, terpenoids and coumarin. Eight different polyphenols (five phenolic acids, vanillic, benzoic, p-coumaric, gallic and syringic acid, and three types of flavonoids, naringenin, catechin and kaempferol) were reported from Ashwagandha. Each part of this plant holds an assortment of different metabolites, and the metabolite concentrations vary among the different chemotypes. Ashwagandha has been used for a variety of ailment since a long time by traditional medicinal systems. It has been used for a range of diseases such as diabetes, emaciation, arthritis and rheumatoid arthritis-related inflammations, some kinds of seizures, diarrhoea, dermatitis and insect bite and specially used in the treatment of nervous disorder. The importance of Ashwagandha in medicinal treatments has attracted the attention of a large number of scientists; as a result, numerous experiments have been carried out, which have verified the therapeutic properties of Ashwagandha. Further, the efforts are being taken for the breeding strategies via conventional breeding as well as plant tissue culture techniques and gene transformation for the improvement of withanolide contents. This chapter gives an extensive insight on the various aspects such as basic introduction, classification, botanical description, bioactive molecules, medicinal properties and commercially available products. Furthermore, this chapter narrates the several breeding approaches for the improvement of withanolide contents of Ashwagandha.
Obesity can disrupt the fertility processes in both men and women by various mechanisms, chiefly including hormonal derangements on sex steroids and a dysmetabolic milieu characterized by an insulin-resistant state. In addition, low-grade inflammation and a consequent lipotoxic state may impair structural and functional mitochondrial physiology, thereby oocyte function and sperm quality in women and men, respectively. In women, obesity may also impair endometrial receptivity that became an important factor explaining the failure of assisted reproductive technologies in these women. The polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility in women. Obesity tends to favor the development of PCOS in adolescent girls and worsens the phenotype of adult affected women, by increasing the hyperandrogenic state and ovarian dysfunction. Moreover, it plays a major role in the development of a dysmetabolic profile. In turn, obesity reduces the potential efficacy of medical treatments of infertility in most of these women. Weight loss may conversely favor ovulation rates and pregnancy rates in these women. This short review summarizes the most important aspects of obesity-related infertility in both men and women, including those affected by PCOS.
There are conflicting reports on the heavy metal levels in human semen with different fertilities. The purpose of this analysis is to merge and analyze the differences of heavy metal lead (Pb), cadmium (Cd), zinc (Zn), and copper (Cu) levels in male semen with normal and low fertilities. All documents in both Chinese and English were collected from the PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) database from inception date to February 19, 2016. We have used RevMan software (version 5.2) for the meta-analysis and Stata software (version 12.0) for the meta-regression and sensitivity analyses. A total of 20 literatures were included in the study. The results of the meta-analysis indicate a significant difference between fertility with three metal ions (Pb, Cd, Zn) while no significant difference with copper, detailed as follows: (i) 10 studies on the lead concentrations with a standardized mean difference (SMD) = 2.07, 95 %CI (0.97, 3.17), P < 0.01; (ii) 13 studies on the cadmium concentrations with an SMD = 0.75, 95 %CI (0.44, 1.07), P < 0.01; (iii) 8 studies on the concentrations of zinc with an SMD = −0.61, 95 %CI (−1.08, −0.14), P < 0.01; and (iv) 9 studies on the copper concentrations with an SMD = 0.42, 95 %CI (−0.29, 1.13), P = 0.247. The results indicate that the men with low fertility have higher semen Pb and Cd levels and lower semen Zn levels; more studies are needed to indicate the association of the semen copper level with fertility.
Obesity can disrupt the fertility processes in both men and women by various mechanisms, chiefly including hormonal derangements on sex steroids and a dysmetabolic milieu characterized by an insulin-resistant state. In addition, low-grade inflammation and a consequent lipotoxic state may impair structural and functional mitochondrial physiology, thereby oocyte function and sperm quality in women and men, respectively. In women, obesity may also impair endometrial receptivity that became an important factor explaining the failure of assisted reproductive technologies in these women. The polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility in women. Obesity tends to favor the development of PCOS in adolescent girls and worsens the phenotype of adult affected women, by increasing the hyperandrogenic state and ovarian dysfunction. Moreover, it plays a major role in the development of a dysmetabolic profile. In turn, obesity reduces the potential efficacy of medical treatments of infertility in most of these women. Weight loss may conversely favor ovulation rates and pregnancy rates in these women. This short review summarizes the most important aspects of obesity-related infertility in both men and women, including those affected by PCOS.
Phytotherapy belongs to the area of complementary and alternative medicine (CAM) and the definition of phytotherapy is the use of plants or plant extracts for medicinal uses. Interest in phytotherapy is growing in both Asian and western countries for its use in the prevention and management of disease, improvement of general health and anti-aging. And also, there are several studies about the efficacy of phytotherapy in urologic diseases like benign prostatic hyperplasia (BPH), erectile dysfunction (ED), late-onset hypogonadism (LOH) and infertility in males. Phytotherapy for BPH including saw palmetto, pygeum, and nettles, is under vigorous research for the therapeutic effect. No solid evidence showing better effective treatment modality for ED than placebo has been found yet for phytotherapy. Recently, a potent NO donor, L-arginine is under research with promising results. Phytotherapy is used by a number of patients with urological disease, and urologists need to have accurate knowledge about phytotherapy as well as keep a cautious approach. The possible effects and side effects should be defined and related to urologic patients by urologists.
Objective:
The main objective of the current study was to observe the ameliorative effect of Withania somnifera on arsenic-induced testicular toxicity by exploring the crucial parameters such as sperm counts, sperm motility, hormonal assay and lipid peroxidation including histopathology.
Materials and methods:
In the present study, arsenic in the form of sodium arsenite was administered orally to male Charles Foster rats for 45 days. Thereafter, ethanolic root extract of Withania somnifera was administered for 30 days to observe its ameliorative effect on male reproductive system.
Results:
The study revealed that after administration of sodium arsenite, there was a decrease in the sperm counts and sperm motility accompanied by an increased incidence of sperm abnormalities and hormonal imbalance leading to infertility. However, after administration of Withania somnifera, there was significant reversal in the parameters denoting that it not only possesses antioxidant and rejuvenating property but also maintains the cellular integrity of testicular cells leading to normal functioning of it.
Conclusion:
The study concludes that Withania somnifera possesses phytoremedial effect. It is one of the best antidotes against arsenic-induced reproductive toxicity.
Our previous works have indicated that the mitochondrion is the primary target of nephrotoxicity induced by andrographolide sodium bisulfate (ASB), but the mechanisms of ASB-induced nephrotoxicity have remained largely unknown. In this study, proteomic analysis was used to explore the changes in the renal mitochondrial proteome in SD rats after treatment with ASB. SD rats were intraperitoneally administered with ASB (100, 600mg/kg/d) for 7 days. Renal impairment was evaluated by pathological observation. Two-dimensional gel electrophoresis (2-DE), as well as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS), was applied for the identification of mitochondrial protein and was validated by Western blotting. Protein-protein interactions were analyzed using a Web-based bioinformatics tool (STRING, version 9.1). Rat kidneys exhibited histopathological changes after treatment with ASB, and 13 proteins were significantly changed, including ES1 protein homolog, heat shock cognate 71kDa protein, peroxiredoxin-1 (Prdx1), cytochrome C oxidase subunit 5B (COX5B), prohibitin (PHB), threonine-tRNA ligase, pyruvate dehydrogenase E1 component subunit beta (PDH-β), voltage-dependent anion-selective channel protein 2 (VDAC2), voltage-dependent anion-selective channel protein 1 (VDAC1), adenylate kinase 2 (KAD2) and others. These data demonstrated that the expression levels of several proteins significantly changed in the mitochondria, and these proteins could be candidate biomarkers for ASB-induced nephrotoxicity.
This study describes optimisation and validation processes for the simultaneous determination of Ag, As, B, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Se, Sn, and Zn in seminal plasma samples by inductively coupled plasma mass spectrometry (ICP-MS) using the octopole reaction system (ORS) collision/reaction cell. Two sample pre-treatment procedures, i.e. digestion and dilution, were explored and compared with regard to linearity, detection and quantification limits obtained on a real sample, and precision. To verify the accuracy of these methods, serum QC materials were used, while spiked seminal plasma pooled samples were used to assess precision and recovery. Although both pre-treatment methods allowed sensitive and reproducible analyses, the method of simple dilution of seminal plasma 1+19 with aqueous solution containing 0.01 mmol L exp-1 EDTA, 0.004% v/v NH3, and 0.07% v/v TritonX-100 was chosen due to the reduced time of analysis and risks of sample contamination. The proposed method was applied for the simultaneous determination of 20 elements in seminal plasma of 76 adult men with suspected infertility, and the results were compared against recent data from the literature. We investigated the element distribution depending on smoking habits and the results of the comparison between 37 smokers and 39 non-smokers showed significantly higher concentrations of Cd in seminal plasma of smokers as well as dependence on increases in the number of cigarettes smoked per day (P=0.004). In addition, our results are the first to provide data for Ag and B concentrations in human seminal plasma.
Ubiquinol-cytochrome-c reductase core protein 2 (UQCRC2) is a component of ubiquinol-cytochrome c reductase complex that is known to correlate with male fertility via spermatogenesis. Simultaneously, nutlin-3a is a small molecule antagonist of mouse double minute 2 repressor (MDM2), activate p53 and induce apoptosis responsible for spermatogenesis. To date, however there are no known effects of nutlin-3a on reproduction. Therefore, present study was designed to investigate the effect of nutlin-3a on male fertility via UQCRC2. In this in vitro trial with mice spermatozoa, we utilized CASA, CTC staining, ATP assay, western blotting, and IVF to measure the main study outcome. The short-term exposure of spermatozoa in nutlin-3a decreases sperm motion kinematics, intracellular ATP production, capacitation, the acrosome reaction, UQCRC2, and tyrosine phosphorylation (TYP) of sperm proteins in a dose-dependent manner. Notably, the decreased UQCRC2 and TYP were associated with reduced sperm kinematics, ATP production, and capacitation, which ultimately led to adverse effects on male fertility such as poor fertilization rates and embryo development. Thus, nutlin-3a may be considered as a potential male contraceptive agent due to its ability to decrease fertility secondary to changes in overall sperm physiology and embryonic development. However, the results of this preliminary study have to be confirmed by additional independent trial.
Traditional Indian systems of medicine use roots of Withania somnifera (W. somnifera) for impotence, infertility treatment, stress, and the aging process. Although W. somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress, the molecular mechanism is not clear.
Our study uses high-resolution Nuclear Magnetic Resonance (NMR) spectroscopy to explore the scientific basis to reveal the pre- and post-treatment efficacy of W. somnifera on seminal plasma of infertile men-which remains unexplored to date.
A total of 180 infertile male patients were administered W. somnifera root powder at the rate of 5g/d for a three-month period. The study included age-matched, healthy men as a control (n=50) group. Proton NMR spectroscopy was used to measure lactate, alanine, glutamate, glutamine, citrate, lysine, choline, glycerophosphocholine (GPC), glycine, tyrosine, histidine, phenylalanine, and uridine in all seminal plasma samples. To appraise infertility levels, we also measured sperm concentration, motility, lipid peroxide, and hormonal perturbation.
W. somnifera therapy repairs the disturbed concentration of lactate, alanine, citrate, GPC, histidine, and phenylalanine in seminal plasma and recovers the quality of semen of post-treated compared to pre-treated infertile men. Serum biochemistry was also improved over post therapy in infertile men. Our findings reveal that W. somnifera not only reboots enzymatic activity of metabolic pathways and energy metabolism but also invigorates the harmonic balance of seminal plasma metabolites and reproductive hormones in infertile men.
The results suggest that W. somnifera may be used as an empirical therapy for clinical management and treatment of infertility.
Infertility is a significant problem, affecting up to 15% of couples of reproductive age. Impairment of the spermatozoal function or its structure is the result of the imbalance between oxidants and antioxidants both in spermatozoa, and seminal plasma.
Reactive oxygen species (ROS), when in low, physiological concentrations, trigger various signal pathways leading to capacitation, hyperactivated motility and acrosomal reaction in spermatozoa. Increased production of ROS is associated with a variety of pathological conditions, both local and systemic. ROS can oxidate all sorts of molecules in spermatozoa: nucleic acids, lipids, proteins, carbohydrates… These damages reflect as poor semen quality, decreased motility and reduced fertilization potential.
Various parameters of oxidative stress (rate of lipid peroxidation, level of ROS, ROS-TAC score, indicators of DNA damage, activity of antioxidante enzymes) should be considered for implementation into clinical assesment of infertile couples. The aetiology of some cases of infertility may be genetic (certain variations of the genes encoding glutathione S-transferase and phospholipid hydroperoxide glutathione peroxidase, have been associated with male infertility). Assesing the level of DNA damage is especially beneficial for couples undergoing artificial reproductive techniques: a fertilized oocyte has limited potentials for repairing the damage of the genetic material coming from the male donor – a newly formed zygote may carry various mutations which can lead to premature death of the embryo, or pathologic conditions in the offspring.
One of the treatment options could be antioxidant supplementation. Various drugs (some of them originating from traditional medicines) have been proposed, but the results are still dubious.
Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients.
To investigate the impact of Withania somnifera roots on semen profile, oxidative biomarkers, and reproductive hormone levels of infertile men.
Prospective study.
Departments of Biochemistry and Urology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India.
Seventy-five normal healthy fertile men (control subjects) and 75 men undergoing infertility screening.
High-performance liquid chromatography assay procedure for quantization of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma were estimated by standard spectrophotometric procedures. Estimation of T, LH, FSH, and PRL in blood serum by RIA methods.
Before and after the treatment, seminal plasma biochemical parameters, antioxidant vitamins, and serum T, LH, FSH, and PRL levels were measured.
Withania somnifera inhibited lipid peroxidation and protein carbonyl content and improved sperm count and motility. Treatment of infertile men recovered the seminal plasma levels of antioxidant enzymes and vitamins A, C, and E and corrected fructose. Moreover, treatment also significantly increased serum T and LH and reduced the levels of FSH and PRL.
The treatment with W. somnifera effectively reduced oxidative stress, as assessed by decreased levels of various oxidants and improved level of diverse antioxidants. Moreover, the levels of T, LH, FSH and PRL, good indicators of semen quality, were also reversed in infertile subjects after treatment with the herbal preparation.
Infertility affects about 15 per cent married couples half of which may be attributed to men with low sperm motility (asthenozoospermia), low sperm count (oligozoospermia) or abnormal sperm morphology (teratozoospermia). As mitochondria are the energy source for initiation, differentiation and function of the germ cells, mutation in mitochondrial genome can impair the formation of mature spermatozoa. Mutations in mitochondrial genome are identified in patients with fertility problems. However, mitochondria are also both the source and target of reactive oxygen species (ROS). ROS are normally generated at low levels by human spermatozoa in order to perform its physiological function. However, if the generation of these reactive free radicals overwhelm the antioxidant defense system, this can lead to oxidative stress, which is characterized by mitochondrial and nuclear genome damage. So both ROS and mtDNA mutations are considered to be the major aetiological factors in a variety of human diseases including male infertility. Identification of novel mutations in mtDNA of infertile patients with supraphysiological levels of ROS are considered to be important to gain better understanding of the aetiology of idiopathic infertility. Early detection and prompt antioxidant therapy can prevent ROS induced DNA damage. This has far reaching impact if such men opt for assisted reproductive technology (ART)/in vitro fertilization.
To assess the effect of leukocytospermia and semen processing on sperm DNA and mitochondria.
Twenty-two patients with and 41 without leukocytospermia were included. Sperm DNA fragmentation was assessed by the Comet assay, and mitochondrial activity by a colorimetric method for active mitochondria. Semen was processed using Percoll, and motility, DNA fragmentation, and mitochondrial activity were analyzed pre- and post-processing.
No differences were observed in age, abstinence, volume, sperm morphology, progressive motility, concentration, and vitality (p>0.10). Variables were grouped according to time (pre- vs post-processing) and group (leukocytospermia vs non-leukocytospermia) because no interactions could be observed. Leukocytospermia was associated to increased DNA fragmentation, while semen processing led to a decrease in DNA fragmentation and to increased mitochondrial activity.
While semen processing selects sperm with higher rates of DNA integrity independent of the presence or absence of leukocytes in semen, samples without leukocytospermia present more sperm without DNA fragmentation. Semen processing also selects sperm with higher mitochondrial activity.
To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility.
Prospective study.
Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India.
Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening.
High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL.
Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured.
Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment.
Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.
The present investigation was undertaken to assess the role of Mucuna pruriens in infertile men who were under psychological stress. Study included 60 subjects who were undergoing infertility screening and were found to be suffering from psychological stress, assessed on the basis of a questionnaire and elevated serum cortisol levels. Age-matched 60 healthy men having normal semen parameters and who had previously initiated at least one pregnancy were included as controls. Infertile subjects were administered with M. pruriens seed powder (5 g day(-1)) orally. For carrying out morphological and biochemical analysis, semen samples were collected twice, first before starting treatment and second after 3 months of treatment. The results demonstrated decreased sperm count and motility in subjects who were under psychological stress. Moreover, serum cortisol and seminal plasma lipid peroxide levels were also found elevated along with decreased seminal plasma glutathione (GSH) and ascorbic acid contents and reduced superoxide dismutase (SOD) and catalase activity. Treatment with M. pruriens significantly ameliorated psychological stress and seminal plasma lipid peroxide levels along with improved sperm count and motility. Treatment also restored the levels of SOD, catalase, GSH and ascorbic acid in seminal plasma of infertile men. On the basis of results of the present study, it may be concluded that M. pruriens not only reactivates the anti-oxidant defense system of infertile men but it also helps in the management of stress and improves semen quality.
Few nonphagocytic cells are known to generate reactive oxygen intermediates. Based on horseradish peroxidase-dependent, catalase-inhibitable oxidation of fluorescent scopoletin, seven human tumor cell lines constitutively elaborated H2O2 at rates (up to 0.5 nmol/10(4) cells/h) large enough that cumulative amounts at 4 h were comparable to the amount of H2O2 produced by phorbol ester-triggered neutrophils. Superoxide dismutase-inhibitable ferricytochrome c reduction was detectable at much lower rates. H2O2 production was inhibited by diphenyleneiodonium, a flavoprotein binder (concentration producing 50% inhibition, 0.3 microM), and diethyldithiocarbamate, a divalent cation chelator (concentration producing 50% inhibition, 3 microM), but not by cyanide or azide, inhibitors of electron transport, or by agents that inhibit xanthine oxidase, polyamine oxidase, or cytochrome P450. Cytochrome b559, present in human phagocytes and lymphocytes, was undetectable in these tumor cells by a sensitive spectrophotometric method. Mouse fibroblasts transfected with human tyrosinase complementary DNA made melanin, but not H2O2. Constitutive generation of large amounts of reactive oxygen intermediates, if it occurs in vivo, might contribute to the ability of some tumors to mutate, inhibit antiproteases, injure local tissues, and therefore promote tumor heterogeneity, invasion, and metastasis.
Although semen analysis is routinely used to evaluate the male partner in infertile couples, sperm measurements that discriminate between fertile and infertile men are not well defined.
We evaluated two semen specimens from each of the male partners in 765 infertile couples and 696 fertile couples at nine sites. The female partners in the infertile couples had normal results on fertility evaluation. The sperm concentration and motility were determined at the sites; semen smears were stained at the sites and shipped to a central laboratory for an assessment of morphologic features of sperm with the use of strict criteria. We used classification-and-regression-tree analysis to estimate threshold values for subfertility and fertility with respect to the sperm concentration, motility, and morphology. We also used an analysis of receiver-operating-characteristic curves to assess the relative value of these sperm measurements in discriminating between fertile and infertile men.
The subfertile ranges were a sperm concentration of less than 13.5 x 10(6) per milliliter, less than 32 percent of sperm with motility, and less than 9 percent with normal morphologic features. The fertile ranges were a concentration of more than 48.0 x 10(6) per milliliter, greater than 63 percent motility, and greater than 12 percent normal morphologic features. Values between these ranges indicated indeterminate fertility. There was extensive overlap between the fertile and the infertile men within both the subfertile and the fertile ranges for all three measurements. Although each of the sperm measurements helped to distinguish between fertile and infertile men, none was a powerful discriminator. The percentage of sperm with normal morphologic features had the greatest discriminatory power.
Threshold values for sperm concentration, motility, and morphology can be used to classify men as subfertile, of indeterminate fertility, or fertile. None of the measures, however, are diagnostic of infertility.
Numerous studies have shown the presence of DNA strand breaks in human ejaculated spermatozoa. The nature of this nuclear anomaly and its relationship to patient etiology is however poorly understood. The aim of this study was to investigate the relationship between nuclear DNA damage, assessed using the TUNEL assay and a number of key apoptotic markers, including Fas, Bcl-x, and p53, in ejaculated human spermatozoa from men with normal and abnormal semen parameters. We also determined the nature of the DNA damage by examining the percentage of ejaculated spermatozoa exhibiting DNA damage using the comet assay and by challenging sperm chromatin to attack by micrococcal nuclease S7 and DNase I. We show that TUNEL positivity and apoptotic markers do not always exist in unison; however, semen samples that had a low sperm concentration and poor morphology were more likely to show high levels of TUNEL positivity and Fas and p53 expression. In addition, the DNA damage in ejaculated human sperm is represented by both single- and double-stranded DNA breaks, and access to the DNA is restricted by the compacted nature of ejaculated spermatozoa. This DNA protection is poorer in men with abnormal semen parameters. We propose that the presence of DNA damage is not directly linked to an apoptotic process occurring in spermatozoa and arises due to problems in the nuclear remodeling process. Subsequently, the presence of apoptotic proteins in ejaculated spermatozoa may be linked to defects in cytoplasmic remodeling during the later stages of spermatogenesis.
Multiple shoot cultures of two experimental lines of Withania somnifera plants (RS-Selection-1 and RS-Selection-2) were established using nodal segments as explants. The hormonal combinations of benzyl adenine and kinetin not only influenced their morphogenetic response but also differentially modulated the level of biogeneration of withanolide A in the in vitro shoots of the two lines. Interestingly, withanolide-A, that was hardly detectable in the aerial parts of field-grown Withania somnifera (explant source), accumulated considerably in the in vitro shoot cultures of the plant. The productivity of withanolide A in the cultures varied considerably (ca. 10-fold, 0.014 to 0.14 mg per gram fresh weight) with the change in the hormone composition of the culture media as well as genotype used as source of the explant. The shoot culture of RS-Selection-1 raised at 1.00 ppm of BAP and 0.50 ppm of kinetin displayed the highest concentration of withanolide A in the green shoots of 0.238 g per 100 g dry weight tissue. This was a more analytical concentration keeping in view the isolation yields so far reported from the dried roots of the field-grown plant (ca. 0.015 g per 100 g dry weight), even if isolation losses are considered during purification. The enhanced de novo biogenesis of withanolide A in shoot cultures was corroborated with radiolabel incorporation studies using [2-(14)C] acetate as a precursor. Production of withaferin A was also found in the in vitro shoot cultures. As this compound is a predominant withanolide of native shoots as well and has been already reported to be accumulated in in vitro shoot cultures, its biogeneration observed in these shoot cultures is not discussed in detail.
This paper reviews the possible origin of sperm DNA fragmentation and focuses on the nuclear events associated with spermiogenesis as a potential source of genetic instability and reduced fertilizing potential of the mature male gamete. Recent findings suggest a programmed DNA fragmentation and DNA damage response during the chromatin remodeling steps in spermatids. We also discuss the spermatid DNA repair mechanisms and the possible involvement of condensing proteins, such as transition proteins and protamines, in the process, as this DNA fragmentation is normally not found in late spermatids. We propose that alterations in the chromatin remodeling steps or DNA repair in elongating spermatids may lead to persistent DNA breaks. This vulnerable step of spermiogenesis may provide a clue to the etiology of sperm DNA fragmentation associated with infertility in humans. This vulnerability is further emphasized given the haploid character of spermatids that must resolve programmed double-stranded breaks by an error-prone DNA repair mechanism. Therefore, spermiogenesis has probably been overlooked as an important source of genetic instability.
A flame-AAS method was evaluated for its analytical accuracy in the determination of serum copper and serum zinc in commercially available reference materials: Cation-Cal, Seronorm, and Contox for Cu and Zn, and Precilip for Cu. The method includes dilution of serum (1+9) with a water solution of 6% (v/v) 1-butanol and calibration with standards containing a mixture of Cu and Zn in 0.5% (v/v) HCl, diluted in the same way. The detection limits (3 σ) of the method were 1.27 μg/L of Cu and 0.78 μg/L of Zn, the day-to-day precisions (coefficients of variation) of duplicate determinations in 152 human serum samples were in the range 1.7-4.5% at 831-1772 μg/L of Cu and 1.2-3-9% at 601-1245 μg/L of Zn, and the recoveries (mean±SD) were 100.2±1.1% of Cu and 99.6±0.9% of Zn. The results obtained for three out of the four reference materials were in good agreement with the certified values for both Cu and Zn. On the other hand, the precision and the accuracy of the Cu and Zn results obtained for Contox were poor, probably due to the nonhomogeneity of this lyophilized reference material following its reconstitution with water, and possibly unreliable certified values.
The ability of Sertoli cells harvested from 18-day-old Sprague-Dawley rats to generate reactive oxygen species (ROS) occurs under unstimulated and stimulated conditions. Thus, the generation of ROS and its regulation by stimulating and inhibiting compounds was determined as a lucigenin-dependent chemiluminescence reaction. According to the data, ROS generation was influenced by different cell preparation conditions-stimulating substances such as PMA, FMLP, C5a, A23187, and scavestrogens characterized by antioxidant, radical-scavenging properties. The mechanical homogenization during cell preparation procedures leads to an increase of ROS generation. ROS generation of Sertoli cells was followed by elected substances in the following rank order of efficacy: PMA > FMLP ≥ C5a > Ca-ionophore A23187. The registered inhibiting effects of the scavestrogens J811 and J861 were significant. The measured CL counts decreased at 72 and 77%, respectively, of control experiments done without scavestrogens. The generation of reactive oxygen species in Sertoli cells and especially the increase in oxygen free radicals and their effects on cellular structures of spermatids are directly involved in inducing morphological alterations. Sertoli cells play an important role in spermatogenesis. The measurements of ROS may have clinical relevance in the evaluation of infertility.
The present study was undertaken to assess the beneficial role of M. puriens in infertile men (n= 60) [normozoospermic infertilemen (n= 20), oligozoospermic (n= 20) and asthenozoospermic (n= 20)]. Age-matched 60 healthy men having normal semen parameters and who had previously initiated at least one pregnancy earlier were included as controls. Infertile subjects were prescribed M. puriens seed powder (5 g/day) orally for three months. For carrying out morphological and biochemical analysis, semen samples was ...
To investigate the prevalence of high levels of sperm DNA damage among men from infertile couples with both normal and abnormal standard semen parameters.
A total of 350 men from infertile couples were assessed. Standard semen analysis and sperm chromatin structure assay (SCSA) were carried out.
Ninety-seven men (28% of the whole study group) had a DNA fragmentation index (DFI)> 20%, and 43 men (12%) had a DFI>30%. In the group of men with abnormal semen parameters (n = 224), 35% had a DFI>20%, and 16% had a DFI>30%, whereas these numbers were 15% and 5%, respectively, in the group of men with normal semen parameters (n=126). Men with low sperm motility and abnormal morphology had significantly higher odds ratios (ORs) for having a DFI>20% (4.0 for motility and 1.9 for morphology) and DFI>30% (6.2 for motility and 2.8 for morphology) compared with men with normal sperm motility and morphology.
In almost one-third of unselected men from infertile couples, the DFI exceeded the level of 20% above which, according to previous studies, the in vivo fertility is reduced. A significant proportion of men with otherwise normal semen parameters also had high sperm DNA damage levels. Thus, the SCSA test could add to explaining causes of infertility in cases where semen analysis has not shown any deviation from the norm. We also recommend running the SCSA test to choose the appropriate assisted reproductive technique (ART).
The use of antioxidants in treatment of infertile men has been suggested, although the evidence base for this practice is unclear. A systematic review of randomized studies was conducted to evaluate the effects of oral antioxidants (vitamins C and E, zinc, selenium, folate, carnitine and carotenoids) on sperm quality and pregnancy rate in infertile men. MEDLINE, EMBASE, Cochrane Library and CINAHL were searched for relevant trials published from respective database inception dates to May 2009. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Seventeen randomized trials, including a total of 1665 men, were identified, which differed in the populations studied and type, dosage and duration of antioxidants used. Only two-thirds of the studies (11/17) reported using allocation concealment and three studies (18%) used intention-to-treat analysis. Despite the methodological and clinical heterogeneity, 14 of the 17 (82%) trials showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy. Ten trials examined pregnancy rate and six showed a significant improvement after antioxidant therapy. The use of oral antioxidants in infertile men could improve sperm quality and pregnancy rates. Adequately powered robust trials of individual and combinations of antioxidants are needed to guide clinical practice.
Oxidative stress (OS) has been recognized as one of the most important cause of male infertility. Despite the antioxidant activity of seminal plasma, epididymis and spermatozoa, OS damages sperm function and DNA integrity. Since antioxidants suppress the action of reactive oxygen species, these compounds have been used in the medical treatment of male infertility or have been added to the culture medium during sperm separation techniques. Nevertheless, the efficacy of such a treatment has been reported to be very limited. This may relate to: (i) patient selection bias; (ii) late diagnosis of male infertility; (iii) lack of double-blind, placebo-controlled clinical trial; and/or (iv) use of end-points that are not good markers of the presence of OS. This review considers the effects of the main antioxidant compounds used in clinical practice. Overall, the data published suggest that no single antioxidant is able to enhance fertilizing capability in infertile men, whereas a combination of them seems to provide a better approach. Taking into account the pros and the cons of antioxidant treatment of male infertility, the potential advantages that it offers cannot be ignored. Therefore, antioxidant therapy should remain in the forefront of preventive medicine, including human reproductive medicine.
The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumours, a new and important cause has been identified: oxidative stress. Oxidative stress is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body. It is a powerful mechanism that can lead to sperm damage, deformity and eventually, male infertility. This review discusses the physiological need for ROS and their role in normal sperm function. It also highlights the mechanism of production and the pathophysiology of ROS in relation to the male reproductive system and enumerate the benefits of incorporating antioxidants in clinical and experimental settings.
Assessment of sperm DNA damage has been suggested as a negative predictor of fertility potential. Multiple pathological factors acting at both the intra-testicular and post-testicular levels may contribute to sperm DNA damage. The relative contribution of each of these factors in an individual with high DNA damage (>30%) is unclear. The management of patients with elevated DNA damage is also challenging. The purpose of our retrospective study was to evaluate the clinical course of patients with sperm DNA damage over 30% and to assess the effect of non-specific (oral antioxidant) and cause-specific treatments on the quality of their sperm DNA. Results of our retrospective study suggest that the evaluated group with high DNA damage was diagnostically heterogeneous and comprised patients with varicoceles, bacteriospermia and idiopathic infertility. A three month course of antioxidant therapy reduced sperm DNA damage in only 30/61 (49%) patients with significant improvement between the initial and post-treatment DNA Fragmentation Index (DFI) results (46.8%+/-14.1 vs. 36.7%+/-16.6, p < .001). The positive effect of antioxidants could be age-dependent, as patients older that 40 years of age showed no improvement after such treatment. The cause-specific treatments showed superior results compared to antioxidants alone. Improvement was observed in 7/9 (78%) of patients after surgical varicocele repair between the initial and post-treatment DFI results (44.7%+/-12.8 vs. 28.4%+/-9.5, p < .03). The majority of the patients 13/14 (93%) with bacteriospermia had improvement in sperm DFI results after antibiotic treatment (50.4%+/-19.1 vs. 38.6%+/-18.7, p < .001).
Accurate transmission of information coded in the sperm genome is vital to the pre- and post-natal development of the offspring. Recent advances in reproductive biology have proposed evaluation of sperm DNA integrity as an important assessment tool to infer the presence of DNA strand breaks, numerical abnormalities in sperm chromosome complement, and alterations in the epigenetic regulation of the paternal genome. Oxidative stress (OS), characterized by increased free radicals, may lead to the production of apurine sites, apyrimidine sites, oxidation of nucleotides of sperm genome. This study was performed to assess the impact of OS on DNA integrity in sperms. 52 infertile men [oligozoospermic-13, asthenozoospermic-15, teratozoospermic-19, oligoasthenoteratozoospermic-5] and 20 fertile controls were investigated for products of lipidperoxides as malondialdehyde; antioxidants such as superoxide dismutase, catalase and glutathione in seminal plasma by biochemical methods. DNA integrity of the sperms was analyzed by visual scoring method in which the comets were graded into 4 categories (A-D) on the basis of their tail length indicative of increasing levels of DNA damage. Significant increase in DNA damage (higher number of sperms in group D) in cases (oligozoospermic (O)-20%, asthenozoospermic (A)-24%, teratozoospermic (T)-28%, OAT-43%) as compared to controls (8%) was found. Increased malondialdehyde levels, abnormal sperm morphology and higher DNA damage were observed in the cases. The antioxidants superoxide dismutase, catalase and glutathione had a positive association with sperm count and motility while a negative association with the percentage of dead sperms and abnormal morphology was observed. This study highlights the influence of low antioxidants on sperm genome integrity and indicates sperm DNA integrity as a better and more reliable prognostic tool for infertility evaluation than simple quantitative and morphologic evaluation of spermatozoa.
The study consisted of 35 male subjects attending an andrology clinic. The subjects all had poor sperm parameters that could not be attributed to any known medical cause. The objective was to evaluate the relation between various seminal characteristics (volume, total sperm count, sperm viability, proportion of progressively motile sperm, and different sperm morphology) and the blood concentrations of lead, cadmium, mercury, copper, and zinc. The mean blood concentrations of lead, mercury, copper, and zinc were within the normal values; cadmium concentration (1.35 micrograms/L) was much higher than the norms. Asthenozoospermic subjects had significantly (p less than .025) higher blood cadmium levels than normozoospermic subjects. No significant differences were noted between the two groups for mean concentration of mercury, zinc, and copper in blood. Significant correlations were observed between blood cadmium levels and volume of semen, midpiece defects, and immature forms of spermatozoa. High blood cadmium levels may have an effect on spermatogenesis. Possible reasons for the high blood cadmium levels among the subjects are discussed.
Eighty infertile men and 38 men of known fertility were studied for investigation of both the importance of zinc, copper, cadmium, and lead to fertility and the possible interrelationships between these trace elements. The infertile men had higher mean concentrations of plasma copper than those of proven fertility. The difference was statistically significant (P less than 0.01) but was of small magnitude (approximately 1.5 mumol mean difference). The concentrations of plasma zinc, erythrocyte zinc, whole blood lead and cadmium, and seminal plasma zinc and copper did not differ significantly between infertile and fertile men. There was a significant positive relationship between sperm density and seminal plasma zinc concentration in the fertile, but not in the infertile, men. The infertile men with antisperm antibodies or counts greater than 20 million/ml had significantly higher mean levels of seminal plasma zinc than infertile men with oligospermia. The higher semen zinc in these two groups may reflect an abnormal fragility of the spermatozoa, resulting in the release of zinc, but the absence of significant overall differences between fertile and infertile men suggests that measurement of the concentration of zinc in plasma or zinc and copper in seminal plasma has little value in the routine investigation of infertility.
In the early stages of apoptosis changes occur at the cell surface, which until now have remained difficult to recognize. One of these plasma membrane alterations is the translocation of phosphatidylserine (PS) from the inner side of the plasma membrane to the outer layer, by which PS becomes exposed at the external surface of the cell. Annexin V is a Ca2+ dependent phospholipid-binding protein with high affinity for PS. Hence this protein can be used as a sensitive probe for PS exposure upon the cell membrane. Translocation of PS to the external cell surface is not unique to apoptosis, but occurs also during cell necrosis. The difference between these two forms of cell death is that during the initial stages of apoptosis the cell membrane remains intact, while at the very moment that necrosis occurs the cell membrane looses its integrity and becomes leaky. Therefore the measurement of Annexin V binding to the cell surface as indicative for apoptosis has to be performed in conjunction with a dye exclusion test to establish integrity of the cell membrane.
Gold injected under the form of anti-rheumatoid polyarthritis soluble solutions provokes, as observed by electron microscope, a deposit of crystalline micro-needles in different tissues, like in cells of adrenal and suprarenal glands, in Leydig cells of the testicles, in isolated thyrocytes and in thyroid endothelial cells. They are present as bundles, often of incurvated type, of high electron-density, present in lysosomes, which contain moreover a hyaline, emptied vesicle. These structures are named "aurosomes". The microanalysis, using the MS 46 (Cameca) and the Camebax (MBX) demonstrates that these crystalline structures are composed by gold associated with sulphur, and not with phosphate.
Thymocyte apoptosis is one of the best characterized experimental models of apoptosis that can be induced by a variety of stimuli such as glucocorticoids, ionizing radiation, antibodies, and toxins. Recently, it has been suggested that oxidative stress is a common mediator of apoptosis. However, little is known about the production and possible function of reactive oxygen intermediates (ROI) in thymocytes. We used a highly sensitive flow cytometric assay with the hydrogen peroxide-sensitive dye, 2',7'-dichlorofluorescin diacetate (DCFH-DA), to measure intracellular ROI production in rat thymocytes, to study its primary sources, and to compare ROI levels in normal and apoptotic thymocytes. Apoptosis was induced by incubating the cells in the presence or absence of dexamethasone (Dex) at 37 degrees C in vitro. Normal thymocytes spontaneously produced significant amounts of ROI. Catalase or superoxide dismutase did not affect this intracellular fluorescence, presumably due to their failure to penetrate into the cells. However, N-acetyl-L-cysteine significantly attenuated the fluorescence in a dose-dependent manner. Significant inhibition of the intracellular fluorescence was also observed by addition of N-nitro-L-arginine methyl ester (L-NAME), that could not be reversed by L-arginine. The addition of N-nitro-D-arginine methyl ester (D-NAME) also caused considerable inhibition. This indicates that the inhibition by L-NAME or D-NAME is due to a direct scavenging effect, and nitric oxide production is not likely to be involved. In contrast to neutrophils and macrophages whose superoxide anions are released from membrane-bound NADPH oxidase, the production of ROI in thymocytes is likely to originate mainly from mitochondria, as indicated by the inhibitory effect of the addition of rotenone or antimycin A. The addition of lymphocyte simulators phytohemagglutinin (PHA), concanavalin A (Con A), or phorbol 12-myristate 13-acetate (PMA) enhanced intracellular fluorescence of thymocytes. This increase was abrogated by addition of rotenone or antimycin A. The ROI production was decreased with time after incubation of the thymocytes for 1, 3, and 6 h in vitro. The appearance of apoptosis of thymocytes in vitro, as indicated by DNA content of cells by flow cytometry and DNA ladder formation in agarose gel electrophoresis, was delayed, as compared to the time course of the decreased ROI production. The addition of Dex to the culture medium accelerated both of these processes. The results suggest that a decreased spontaneous production of ROI in thymocytes precedes the spontaneous in vitro apoptosis and Dex exaggerates these changes.
Semen analysis is part of the routine assessment of infertile couples. WHO defines a sperm concentration above 20x10(6) per mL seminal fluid as normal. We studied the association between semen quality and the probability of conception in a single menstrual cycle in Danish couples with no previous reproductive experience.
In 1992-94, we invited 52,255 trades-union members aged 20-35 years, who lived with a partner and had no children to take part in the study; 430 couples agreed. The couples discontinued use of contraception, and were foll