Oxidative stress status and sperm DNA fragmentation in fertile and infertile men

Evidence suggests that disturbing the balance between reactive oxygen species levels and antioxidant contents in seminal plasma leads to oxidative stress resulting in male infertility. This study was carried out to identifying clinical significance of seminal oxidative stress and sperm DNA fragmentation in treatment strategies of male infertility in southwest Iran. Sperm parameters, lipid peroxidation and activity of antioxidant enzymes were assessed in fertile (n = 105) and infertile (n = 112) men. Malondialdehyde (MDA) levels in seminal plasma were found to be higher significantly (p < .001) in patients. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in seminal plasma were significantly (p < .001) lower in infertile men. Significant negative correlations were observed between MDA levels and sperm motility and normal morphology. Spermatozoa with fragmented DNA were higher (p < .001) in infertile men and significantly correlated with MDA levels and SOD and GPx activities. MDA of 4.2 nmol/ml, SOD of 4.89 U/ml and GPx of 329.6 mU/ml were optimum cut‐off limits to discriminate infertile patients from fertile men. The results show the leading role of oxidative stress in aetiology of male infertility in southwest Iran and indicate that evaluation of seminal antioxidant status and DNA integrity can be helpful in men attending infertility clinics during fertility assessment.     

Seminal plasma oxytocin and oxidative stress levels in infertile men with varicocele

This study aimed to assess seminal plasma oxytocin (OT) and oxidative stress (OS) levels in infertile men with varicocele (Vx). A total of 131 men were divided into fertile men (n = 20), fertile men with Vx (n = 17), infertile men without Vx (n = 40) and infertile men with Vx (n = 54). OT, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated in seminal plasma. Mean levels of seminal OT, MDA were significantly decreased, and the mean level of GPx was significantly increased in fertile men with/without Vx compared with infertile men with/without Vx. Mean levels of OT, MDA were increased, and mean level of GPx was significantly decreased in Vx grade III cases compared with Vx grades I, II cases and in bilateral Vx cases compared with unilateral Vx. There was significant negative correlation between seminal OT with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. It is concluded that seminal OT is significantly decreased in fertile men with/without Vx compared with infertile men with/without Vx. Seminal OT demonstrated significant negative correlation with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. Seminal OT is associated with Vx grade and its bilaterality.     

Interleukin-6 (IL-6) in seminal plasma of infertile men, and lipid peroxidation of their sperm

Concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in seminal fluid, as well as levels of sperm lipid membrane peroxidation, were investigated in fertile and infertile men. Semen samples, obtained by masturbation from 37 infertile and 14 fertile men, were examined for the presence of TNF-alpha and IL-6. The level of lipid peroxidation of the sperm membrane was measured by determining malondialdehyde (MDA) formation. The correlation between the IL-6 and the TNF-alpha concentrations in seminal plasma with the levels of lipid peroxidation of the sperm membranes was statistically evaluated. The IL-6 concentration in seminal plasma of infertile men was significantly higher than that of fertile men (p < .05). Similarly, the level of membrane lipid peroxidation was higher for the semen of infertile men than that of fertile men (p < .001). A significant positive correlation was found between IL-6 levels in seminal plasma and membrane sperm lipid peroxidation (p < .002), but not between this parameter and TNF-alpha levels in seminal plasma. These findings suggest a possible association between IL-6 seminal plasma levels and lipid peroxidation of sperm membrane. Stimulation of reactive species production by human sperm and leucocytes, induced by the high levels of IL-6, could explain these results.     

Normal sperm parameters per se do not reliably account for fertility: A case–control study in the real-life setting

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.     

Decreased prostate-specific membrane antigen levels in the seminal plasma of oligoasthenoteratozoospermic men

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with glutamate carboxypeptidase activity. However, its precise function in the prostate, prostasomes and seminal plasma with regard to male fertility remains unknown. This study was conducted to investigate the seminal plasma PSMA levels in fertile men and patients with oligoasthenoteratozoospermia (OAT) and to analyse its association with sperm parameters. Twenty fertile men and twenty patients admitted at the urology clinic of our institution with the diagnosis of OAT were included in the study. Following semen analysis, seminal plasma was isolated from semen ejaculates. PSMA concentrations in the seminal plasma were determined by ELISA. The correlations between seminal PSMA concentrations and semen parameters were statistically analysed. Seminal plasma PSMA concentration was significantly lower in OAT patients compared to fertile controls (p < .01). In fertile men, PSMA concentration was significantly correlated with the sperm concentration (r = −.481, p < .05), whereas in the patient group no statistically significant correlation was found between the sperm parameters and seminal PSMA level. This is the first study in the literature to investigate PSMA levels in the seminal plasma from infertile men. Decreased levels of seminal plasma PSMA might suggest a role for compromised prostasome function in the pathogenesis of OAT syndrome.     

Assessment of seminal granulysin in infertile men with varicocele

Varicocele has a common association with male infertility, but its exact role is still debated. Apoptosis has been suggested as one of the mechanisms of varicocele‐associated infertility. Granulysin is a molecule that plays a role in apoptosis with no previous study about its role in male infertility. This case‐controlled study aimed to assess seminal plasma granulysin level in infertile patients with varicocele. This study involved 90 men that were allocated into fertile normozoospermic men (n = 20), infertile men without varicocele (n = 30) and infertile men with varicocele (n = 40). These men were subjected to history taking, clinical examination, semen analysis and estimation of seminal granulysin. In general, seminal granulysin level was significantly elevated in infertile men compared with fertile men. Infertile men with varicocele showed significantly higher seminal granulysin compared with infertile men without varicocele, in bilateral varicocele cases and in grade III varicocele. Seminal granulysin level was negatively correlated with sperm concentration, sperm motility, sperm normal forms percentage and testicular volumes. It is concluded that increased seminal granulysin has a negative impact on spermatogenesis in infertile men in general and in infertile men associated with varicocele in particular.     

Effects of lead,cadmium, copper and zinc levels on the male reproductive function

This study aimed to investigate the effects of heavy metals on measures of male fertility. One hundred and two infertile men with occupational exposure and thirty fertile men were included in this study. Blood and urinary levels of lead, cadmium, zinc and copper were measured by atomic absorption spectrophotometry. Semen parameters and a motile sperm organelle morphology examination were also performed. Measures of hormonal levels, oxidation–reduction potential, DNA fragmentation index and chromatin condensation were assessed for all participants. Heavy metals levels, oxidative stress and DNA quality were significantly higher in the infertile group compared to controls. FSH and testosterone levels were lower in the infertile group. A urinary cadmium level was positively associated with abnormal sperm morphology (r = .225, p < .05). Normal morphology was inversely correlated with the duration of the exposure (r = −.227, p = .022). The blood lead level was positively related to the level of testosterone (r = .223, p = .031). Cadmium and lead blood levels were positively correlated with the level of chromatin decondensation (r = .528, p < .001; r = .280, p = .017). Our study showed that occupational exposure to heavy metals is very harmful to reproductive health. DNA quality and oxidative stress investigations must be recommended for reprotoxic exposed patients prior to in vitro fertilisation treatment.     

Seminal androgens,oestradiol and progesterone in oligoasthenoteratozoospermic men with varicocele

This study aimed to assess seminal androgens, oestradiol, progesterone levels in oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). In all, 154 men with matched age and body mass index were investigated that were divided into healthy fertile controls (n = 35), OAT men with Vx (n = 55), OAT men without Vx (n = 64). They were subjected to assessment of semen parameters, seminal levels of testosterone (T), androstenedione (A), 5α‐androstane‐3 α,17 β‐diol (3 α‐diol), oestradiol (E₂), 17‐hydroxyprogesterone (17‐OHP) and progesterone (P). Seminal levels of T and A were significantly decreased where seminal levels of 3 α‐diol, E₂, 17‐OHP, P were significantly higher in OAT men with/without Vx compared with fertile controls. Sperm count, sperm motility and sperm normal forms percentage demonstrated significant positive correlation with seminal T and A and significant negative correlation with seminal 3 α‐diol, E₂, P. It is concluded that in fertile men, seminal T and A are significantly increased and seminal 3 α‐diol, E₂, 17‐OHP, P are significantly decreased compared with infertile OAT men with/without Vx. Association of Vx demonstrated a nonsignificant influence on these hormonal levels in OAT cases. Sperm count, sperm motility and sperm normal forms demonstrated significant positive correlation with seminal T, A and significant negative correlation with seminal 3 α‐diol, E₂, P.     

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

Background

Growing evidence indicates that oxidative stress can be a primary cause of male infertility. Non-enzymatic antioxidants play an important protective role against oxidative damages and lipid peroxidation. Human seminal plasma is a natural reservoir of antioxidants. The aim of this study was to determine glutathione (GSH) concentrations, trace element levels (zinc and selenium) and the lipid peroxidation end product, malondialdehyde (MDA), in the seminal plasma of men with different fertility potentials.

Methods

Semen samples from 60 fertile men (normozoospermics) and 190 infertile patients (74 asthenozoospermics, 56 oligozoospermics, and 60 teratozoospermics) were analyzed for physical and biochemical parameters. Zinc (Zn) and selenium (Se) levels were estimated by atomic absorption spectrophotometry. Total GSH (GSHt), oxidized GSH (GSSG), reduced GSH (GSHr) and MDA concentrations were measured spectrophotometrically.

Results

Zn and Se concentrations in seminal plasma of normozoospermics were more elevated than the three abnormal groups. Nevertheless, only the Zn showed significant differences. On the other hand, Zn showed positive and significant correlations with sperm motility (P = 0.03, r = 0.29) and count (P < 0.01, r = 0.49); however Se was significantly correlated only with sperm motility (P < 0.01, r = 0.36). GSHt, GSSG and GSHr were significantly higher in normozoospermics than in abnormal groups. We noted a significant association between seminal GSHt and sperm motility (P = 0.03). GSSG was highly correlated to sperm motility (P < 0.001) and negatively associated to abnormal morphology (P < 0.001). GSHr was significantly associated to total sperm motility (P < 0.001) and sperm count (P = 0.01). MDA levels were significantly higher in the three abnormal groups than in normozoospermics. Rates of seminal MDA were negatively associated to sperm motility (P < 0.01; r = -0.24) and sperm concentration (P = 0.003; r = -0.35) Meanwhile, there is a positive correlation between seminal lipid peroxidation and the percentage of abnormal morphology (P = 0.008).

Conclusions

This report revealed that decreased seminal GSH and trace element deficiencies are implicated in low sperm quality and may be an important indirect biomarker of idiopathic male infertility. Our results sustain that the evaluation of seminal antioxidant status in infertile men is necessary and can be helpful in fertility assessment from early stages.     

Methylation patterns of methylenetetrahydrofolate reductase gene promoter in infertile males

Errors of folate/homocysteine pathways which are critical for transferring methyl groups have been suggested to affect male fertility. We aimed to evaluate the methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene in infertile males and to investigate the association between MTHFR promoter methylation and success of sperm retrieval. Thirty-five nonobstructive azoospermic and 46 severe oligozoospermic patients constituted the study group and were compared with 49 fertile and/or normozoospermic men. The methylation status was analysed by methylation-specific polymerase chain reaction. MTHFR promoter methylation was detected in infertile men with NOA and SO in the ratio of 48.6% and 58.7%, respectively. Methylation was also observed in 51% of controls. MTHFR promoter was methylated in 65% of men with viable spermatozoon during TESE. No association was found regarding to the profile of MTHFR promoter methylation between both NOA and SO patients and controls (p = .621). There was no relation between the methylation status of MTHFR promoter and low motility and poor morphology (p = .682 and p = .413, respectively). No association was found between MTHFR promoter methylation and presence of viable spermatozoa (p = .382). Our data indicate that the promoter methylation of MTHFR gene may not be associated with male infertility.     

Cytochrome P450‐2D6*4 polymorphism seminal relationship in infertile men

This study aimed to assess cytochrome (CY) P450‐2D6*4 polymorphism relationship with semen variables in infertile men. In all, 308 men were included; fertile normozoospermia (N) (n = 77), asthenozoospermia (A) (n = 70), asthenoteratozoospermia (AT) (n = 75) and oligoasthenoteratozoospermia (OAT) (n = 86). They were subjected to history taking, clinical examination, semen analysis, sperm acrosin activity, seminal malondialdehyde (MDA) and CYP450‐2D6*4 genotyping. CYP450‐2D6*4 wild‐type allele was represented in 76.5% of N, 70% of A, 66.7% of AT and 57.7% of OAT men where homozygous gene mutation was present in 5.9% of N, 20% of A, 26.6% of AT and 26.9% of OAT men, respectively. Sperm acrosin activity, sperm concentration, sperm motility, linear sperm velocity and sperm normal forms were significantly higher, and seminal MDA level was significantly lower in men with CYP450‐2D6*4 wild‐type allele compared with men with homozygous mutation. It is concluded that CYP450‐2D6*4 wild‐type allele has higher frequency where homozygous‐type allele has lower frequency in N men compared with A, AT and OAT men. Sperm acrosin activity index, sperm concentration, sperm motility, linear sperm velocity and sperm normal forms were significantly higher, and seminal MDA level was significantly lower in men with CYP450‐2D6*4 wild‐type allele compared with men with homozygous mutation.     

Relationship of seminal reactive nitrogen and oxygen species and total antioxidant capacity with sperm DNA fragmentation in infertile couples with normal and abnormal sperm parameters

The objective of this study was to investigate the association between the amount of superoxide anion, peroxynitrite as oxidative stress (OS) markers and total antioxidant capacity (TAC) with sperm DNA fragmentation in infertile men with abnormal semen parameters. Semen samples were obtained from 102 infertile couples and divided into groups with normal and abnormal semen parameters according to the World Health Organization (WHO). Peroxynitrite and superoxide anions were detected using spectrofluorometric assays combined with 2,7 dicholorofluorescein (DCF)‐DA and 4‐chloro‐7‐nitrobenzo‐2‐oxa ‐1, 3‐diazole (NBD‐CL). Colorimetric assay was used for evaluation of TAC, while DNA fragmentation was studied by using sperm chromatin dispersion test. Superoxide anion, peroxynitrite and DNA fragmentation were significantly higher in infertile couples with abnormal semen parameters as compared to infertile couples with normal semen (P < 0.01). TAC was significantly lower in infertile men with abnormal semen parameters (P < 0.01). There was also a significant positive correlation between OS markers with sperm DNA fragmentation (r = 0.59, P < 0.01 and r = 0.67, P < 0.01, respectively). We have found that imbalance between superoxide anion and peroxynitrite with antioxidant capacity in infertile men with abnormal sperm parameters is associated with higher sperm DNA fragmentation.     

Association between seminal granulysin and malondialdehyde in infertile men with varicocele and the potential effect of varicocelectomy

This study assessed the seminal plasma granulysin and malondialdehyde (MDA) levels in patients suffering from varicocele-associated infertility prior to and after varicocelectomy. This study was conducted on 34 infertile men with varicocele (group A) and same patients after varicocelectomy (group B) and 32 fertile normozoospermic males (group C). A detailed history taking, clinical examination, scrotal doppler ultrasound for varicocele diagnosis and grading, semen analysis and estimation of seminal granulysin and MDA before and after varicocelectomy were done to all participants. The mean (SD) granulysin and MDA levels in patients with varicocele were higher than in controls with highly significant differences. Post-operatively, there was a significant reduction in mean (SD) granulysin and in MDA level. Basal seminal granulysin positively correlated with basal seminal MDA, abnormal forms and negatively correlated with basal sperm count, concentration, and progressive motility. The receiver operating characteristic curve of seminal granulysin and MDA levels were conducted for discrimination between infertility cases with varicocele and control groups. Excellent AUCs were found for both markers (AUC = 0.971, 0.991 respectively). We concluded that high levels of granulysin and MDA in the semen of infertile males with varicocele negatively impact their spermatogenesis. Varicocelectomy leads to the improvement of semen parameters and significantly decreases seminal plasma granulysin and MDA levels. Hence, seminal granulysin and MDA could be used as a prognostic test in infertile patients with varicocele.     

不育男性精浆总抗氧化能力与精子运动功能的关系

目的:研究不育男性精浆总抗氧化能力(TAC)与精子运动能力和方式之间的关系,探讨精浆TAC水平在男性生育中的临床意义。方法:113例精子密度正常的不育男性,28例正常生育男性作为对照组。精液于37℃液化后采用计算机辅助精液分析(CASA)系统进行精液常规分析,采用比色法进行精浆TAC分析。结果:正常生育组精浆TAC为(19.82±6.33)U,不育男性精子密度正常组精浆TAC为(14.37±8.45)U,不育男性精子密度正常组与正常生育组比较存在显著性差异(P<0.01)。精浆TAC与a级精子百分率(r=0.208,P<0.05)和(a+b)级精子百分率(r=0.231,P<0.05)呈显著正相关,精浆TAC与精子运动参数中的前向性(r=0.200,P<0.05)、直线性(r=0.208,P<0.05)、曲线速度(r=0.189,P<0.05)、直线速度(r=0.210,P<0.05)、平均移动速度(r=0.215,P<0.05)及鞭打频率(r=-0.248,P<0.01)之间有显著的相关性,其中前向性、直线性、直线速度、曲线速度、平均移动速度与TAC呈正相关(P<0.05),而鞭打频率与TAC呈负相关(P<0.01)。精浆TAC与摆动性、侧摆幅度、平均移动角度之间无显著相关。结论:精浆中TAC水平与精子运动能力和运动方式密切相关,适宜的精浆TAC为精子运动提供了良好的外部环境,精浆中过低的TAC水平与精子运动能力下降和运动方式改变有关,可能是引起男性不育的病因之一。精浆中TAC分析可为探讨男性不育的发病机制以及临床用药提供依据。     

Seminal cell-free DNA and sperm characteristic’s: An added biomarker for male infertility investigation

Cell-free DNA (Cf-DNA) fragments may constitute an easy-to-measure molecular tool for guiding the choice of care provided to infertile couples who benefit assisted reproductive technology (ART) programmes. Data on Cf-DNA levels in the seminal plasma of men with sperm alterations are scarce. The objective of the present study was to quantify the presence of Cf-DNA in semen by using a quantitative real-time PCR. We compared men with abnormal sperm characteristics (n = 21) with normospermic controls (n = 21). The PCR assay evidenced significantly higher mean Cf-DNA levels in patients with sperm abnormalities than in controls (2.09 versus 1.18 µg/ml, respectively; p = .0003). The Cf-DNA levels were notably higher in men with azoospermia (3.65 µg/ml, versus 1.34 µg/ml in matched controls; p = .03) and men with teratozoospermia (1.80 µg/ml, versus 1.29 µg/ml in matched controls; p = .008). Our data report a significant association between elevated Cf-DNA levels and sperm abnormalities. These results may open up new diagnostic and prognostic perspectives in male infertility.     

生育与不育男性精浆总抗氧化能力分析

目的:分析生育与不育男性精浆中总抗氧化能力(TAC)及其在男性生育中意义。方法:225例男性不育患者分为6组,分别为:梗阻性无精子症组(n=10),非梗阻性无精子症组(n=42),少精子症组(n=20),弱精子症组(n=78),少弱精子症组(n=57),以及正常精子症组(n=18)。28例正常生育男性作为对照(生育组)。分别采用计算机辅助精液分析(CASA)系统进行精液参数分析,采用比色法检测精浆TAC水平。结果:生育组男性精浆TAC为(19.82±6.33)U,梗阻性无精子症组(1.71±1.33)U,非梗阻性无精子症组(12.73±9.44)U,少精子症组(10.85±6.64)U,弱精子症组(13.88±8.24)U,少弱精子症组(11.20±7.02)U,正常精子症组(18.07±8.73)U;与生育组精浆TAC[(19.82±6.33)U]相比,在各不育症组中,除正常精子症组精浆TAC与生育组差异无显著性外,其余各组均显著低于生育组(P<0.01)。精浆TAC与精子密度(r=0.182,P<0.05)和a级精子(r=0.150,P<0.05)呈显著正相关。结论:精浆中TAC水平与男性不育密切相关,精浆中过低的TAC水平可能是引起男性不育的病因之一。     

Tracing of zinc and iron in experimentally induced varicocele: correlation with oxidative,nitrosative and carbonyl stress

This study was designed to evaluate how varicocele (VCL) can time dependently induce zinc (Zn) and iron (Fe) toxicity in testicular tissue and to analyse the relation between heavy metals toxicity and lipid peroxidation, sperm DNA damage, nitrosative and carbonyl stresses. Twenty‐four mature male Wistar rats were divided into control‐sham and test groups, which were then submitted to experimentally induced VCL. Non‐VCL‐induced rats were considered as control‐sham. The test groups were subdivided into three groups based on the sample collecting date (2, 6 and 8 months after VCL induction). Zn and Fe distribution in testicles, DNA ladder for sperm DNA fragmentation, testicular total antioxidant capacity (TAC), malondialdehyde (MDA), nitrite oxide (NO) and carbonyl groups (CG) were analysed. A significant (p < .05) enhancement in the percentage of tubules with negative tubular repopulation, differentiation and spermiogenesis indices was revealed. The VCL increased Zn and Fe distribution in testicles. The VCL, time dependently, reduced sperm count, motility and enhanced sperm DNA damage (p < .05). The VCL downregulated the testicular TAC and enhanced the MDA, NO and CG contents. Our data showed that the VCL results in intensive Fe and Zn toxicities. Produced Zn‐ and Fe‐mediated‐oxidative stress increases sperm DNA damage associated with NO and CG‐induced stresses.     

Antioxidant activity of seminal plasma in fertile and infertile men

This study was conducted to evaluate and compare the total antioxidant capacity among fertile and infertile men. Thirty infertile patients and 20 fertility-proven healthy donors with normal sperm analysis were included in the study. Total antioxidant capacity, zinc and fructose levels of seminal plasma, and various sperm parameters were compared among fertile controls and idiopathic infertility patients prospectively. The mean antioxidant capacity of fertile controls (2.02 +/- 0.16 mmol/L) was significantly higher than that of the infertile patients group (1.78 +/- 0.23 mmol/L) (p < .01). Furthermore, asthenozoospermic and asthenoteratozoospermic groups had significantly lower mean antioxidant values (1.73 +/- 0.11 and 1.64 +/- 0.13, respectively) when compared to fertile control group (p < .01). The mean fructose level was significantly lower in the fertile control group and mean zinc level was significantly lower in the entire infertile group. On the other hand, antioxidant capacity is positively correlated to sperm motility (p = .001). Decreased antioxidant capacity was associated with impaired sperm function as a result of either increased ROS production or insufficient antioxidant capacity.     

The association of rs11457523 in HSP90AA1 with idiopathic male infertility in the Chinese population

The association of single nucleotide polymorphisms (SNPs) in heat shock protein 90 (HSP90) genes with idiopathic male infertility remains unclear. In this study, the five selected SNPs in HSP90AA1 namely rs10133307, rs10873531, rs11547523, rs11621560 and rs7145597 were genotyped in 116 idiopathic infertile males and 185 ethnically matched fertile males using the Sequenom MassARRAY assay. The role of these SNPs in male infertility was then studied using multiple genetic models. We observed that genotype distribution (p = .028) and allelic frequency (p = .032) of rs11547523 were significantly different between the infertile and fertile groups. In particular, A genotype of rs11547523 was associated with an increased risk of infertility in the allele (OR = 2.508, p = .048), dominant (OR = 2.733, p = .030) and additive models (OR = 0.366, p = .031). However, there were no significant differences in semen parameters including seminal volume (p = .452), sperm concentration (p = .727), total sperm number (p = .588), motility (p = .282) and morphology (p = .975) between A and A/G genotypes of rs11547523. These results indicate that rs11547523 in HSP90AA1 may be associated with idiopathic male infertility in the Chinese population. The outcome of this study contributes to the development of the diagnosis of male infertility.     

Seminal Tumour necrosis factor‐related apoptosis‐inducing ligand and its relationship to infertility in Egyptian patients with varicocele

Germ cell apoptosis has been proposed as one of the mechanisms by which varicocele can influence fertility. The aim of this study was to investigate the relationship between seminal tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) levels and male infertility in patients with varicocele. This study included 112 males: 30 fertile males with varicocele, 44 infertile males with varicocele and 38 healthy fertile control subjects without varicocele. Semen analysis was performed, and serum levels of reproductive hormones were measured. Seminal TRAIL levels in the infertile varicocele group were significantly higher than in the fertile varicocele and the control groups (P = 0.014). A significant negative correlation was found between seminal TRAIL and progressive (P < 0.001) and total motility scores (P < 0.001) in the infertile varicocele group. A significant negative correlation was also detected between seminal TRAIL levels and normal sperm morphology in the fertile varicocele (P = 0.007) and infertile varicocele patients (P = 0.047). Seminal TRAIL was significantly correlated with varicocele grade whether the patients were fertile (P = 0.001) or infertile (P = 0.035). Seminal TRAIL may thus have a potential role in varicocele‐associated male infertility through its negative effect on sperm motility and morphology.