Genetische Aspekte bei Spermatogenesestörungen

The cause for infertility which affects about 10–15% of all couples may be found in approximately half of the cases in the male partners who usually exhibit reduced sperm counts in the ejaculate (i.e. oligozoospermia or azoospermia). The clinically most relevant genetic causes of spermatogenic failure are chromosomal aberrations including Klinefelter’s syndrome and Y chromosomal microdeletions of the AZF loci. Aside from the full clinical picture of cystic fibrosis, mutations in the CFTR gene can cause an isolated obstructive azoospermia without spermatogenic impairment. Genetic investigations should depend on the results of andrological examinations. Chromosomal aberrations are detected more frequently with decreasing sperm counts, where autosomes (e.g. translocations) are predominantly involved in men with oligozoospermia whereas in 10–15% azoospermia is caused by Klinefelter’s syndrome. Classical AZF deletions are found only in men with severe oligospermia or azoospermia and have a prognostic value. In contrast to men with AZFc deletions, carriers of complete AZFa and AZFb deletions have virtually no chance for testicular sperm extraction and a testicular biopsy is not advised. Rare cases of male infertility may be caused by specific syndromes or sperm defects (e.g. globozoospermia and disorders of ciliary structure).     

Relationship of SNP of H2BFWT gene to male infertility in a Chinese population with idiopathic spermatogenesis impairment

The H2B family, member W, testis specific (H2BFWT) gene encodes a testis specific histone that plays a crucial role in reorganization and remodeling of chromatin and epigenetic regulation during spermatogenesis, suggesting that the gene may be involved in spermatogenesis impairment. To test the speculation, the allele and haplotype frequencies of two single-nucleotide polymorphism loci in this gene, ?9C>T and 368A>G, were investigated in 409 infertile patients with idiopathic azoospermia or oligozoospermia and 209 fertile men as controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. As the results, the frequencies of ?9T (52.8% vs. 41.6%, p = 0.009) and 368G (43.0% vs. 32.5%, p = 0.012) were significantly higher in patients than those in controls; after stratifying patients, the significant higher frequencies were still detected in allele ?9T for azoospermia (57.4% vs. 41.6%, p = 0.001) and allele 368G for oligozoospermia (45.4% vs. 32.5%, p = 0.007). The haplotype CA was significantly decreased (22.8% vs. 33.0%, p = 0.006) whereas TG was significantly increased (18.3% vs. 7.2%, p < 0.001) in infertile patients compared with controls. These results indicated that the polymorphism ?9C>T and 368A>G in H2BFWT gene are associated with male infertility with idiopathic azoospermia or oligozoospermia, suggesting that H2BFWT gene might be contribute to susceptibility to spermatogenesis impairment in Chinese population.     

Effect of freezing–thawing process and quercetin on human sperm survival and DNA integrity

We aimed in the first part of our work to study the effect of cryopreservation on the human sperm DNA integrity and the activation of caspase 3, the main apoptosis indicator. In the second part, we were interested in testing the effect of quercetin, as an antioxidant, in preventing sperm damage during the freeze–thawing process. Seventeen semen samples were obtained from 17 men recruited for infertility investigations. Liquefied sperm was cryopreserved using spermfreeze®. Nine of the used samples were divided into two aliquots; the first one was cryopreserved with spermfreeze only (control) and the second one was cryopreserved with spermfreeze supplemented with quercetin to a final concentration of 50 μM. Sperm motility and viability were assessed according to WHO criteria. We used TUNEL assay and the Oxy DNA assay to assess sperm DNA integrity. Activated caspase 3 levels were measured in spermatozoa using fluorescein-labeled inhibitor of caspase (FLICA). Cryopreservation led to a significant increase in sperm DNA fragmentation, DNA oxidation and caspase 3 activation (p < 0.01). Supplementation of the cryopreservation medium with quercetrin induced a significant improvement in post thaw sperm parameters, compared to those of control, regarding sperm motility (p = 0.007), viability (p = 0.008) and DNA integrity (p = 0.02); however, it had no effect on caspase 3 activation (p = 0.3). We conclude that oxidative stress plays a major role in inducing sperm cryodamage but implication of apoptosis in this impairment requires further investigations. Quercetin could have protective effect during cryopreservation but further research is needed to confirm this effect.     

精子端粒长度与特发性男性不育相关

端粒是真核生物染色体末端的多功能特异性DNA-蛋白结构,覆盖在染色体末端,保护基因组的稳定性。端粒在减数分裂过程中起到了十分重要的作用,协助染色体配对、联会、同源重组和分离。精子中的端粒可能在精子的受精能力和胚胎发育中起到重要作用。近年来,端粒与生殖的相关性研究成为一个新的热点,但精子端粒与男性不育间的相关性并不明确。本文采用实时荧光定量PCR方法检测中国特发性男性不育人群(126例)和正常可育男性人群(138例)的精子相对端粒长度,结果发现,特发性男性不育病例的精子平均相对端粒长度(2.894±0.115)低于正常对照组(4.016±0.603),差异具有统计学意义(P=5.097×10^-5);并且精子相对端粒长度与精子密度、精子总数和精子活力都有显著的相关性：精子数量较多和/或精子活力较高,精子相对端粒长度较长。研究结果提示,在中国人群中,精子端粒长度与特发性男性不育具有相关性,精子的端粒长度可能影响精子发生和精子的功能,精子端粒的缩短导致精子数目及活力的降低从而导致男性不育。     

Genetic variants in antioxidant genes are associated with sperm DNA damage and risk of male infertility in a Chinese population

To test the hypothesis that polymorphisms in antioxidant genes are more susceptible to sperm DNA damage and male infertility, we examined 11 single-nucleotide polymorphisms from six antioxidant genes (GPX1, CAT, PON1, NQO1, SOD2/MnSOD, and SOD3) in 580 infertility cases and 580 controls from a Chinese population-based case-control study (NJMU Infertility Study). Genotypes were determined using the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio and 95% confidence interval (CI) were estimated using unconditional logistic regression. The results indicated that the PON1 Arg192Glu (rs662) and SOD2 Val16Ala (rs4880) variant genotypes were associated with a significantly higher risk of male infertility. In addition, subjects carrying variant genotypes of both loci had a twofold (95% CI, 1.42-2.90) increase in the risk of male infertility, indicating a significant gene-gene interaction between these two loci (P for multiplicative interaction=0.045). Moreover, linear regression analysis showed that individuals carrying the PON1 Arg192Glu (rs662) or SOD2 Val16Ala (rs4880) variants have significantly higher levels of sperm DNA fragmentation and 8-OHdG. These data suggest that genetic variations in antioxidant genes may contribute to oxidative sperm DNA damage and male infertility.     

Melatonin Prevents Oxidative Stress and Hepatocyte Cell Death Induced by Experimental Cholestasis

The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500?μg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine aminotransferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of α-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p<0.0001) and a reduction in GSH, GPx, catalase and SOD content (p<0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p<0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis.     

Naissance après ICSI réalisée avec sperme éjaculé, congelé, chez un jeune patient de 21 ans porteur d’un syndrome de Klinefelter homogène

Klinefelter’s syndrome is one of the main genetic causes of male infertility, as it is diagnosed in 11% of patients with azoospermia and 4% of infertile men. This study reports a birth after ICSI performed with ejaculated sperm from a 21-year-old man with homogeneous nonmosaic Klinefelter’s syndrome discovered during assessment of infertility for severe oligozoospermia. Three ICSI were performed for this couple over an 18-month period. Pregnancy was not achieved after the first and second ICSI with fresh ejaculated sperm. At the third ICSI, the patient presented proven azoospermia on the day of the attempt, and frozen-thawed ejaculated spermatozoa were therefore used. A pregnancy was obtained after the transfer of 3 grade A embryos with the birth of a healthy girl. The authors highlight the value of repeated preventive sperm cryopreservation when ejaculated spermatozoa are available in all cases of severe oligozoospermia or cryptozoospermia. They also evaluated the quality (DNA fragmentation, ploidy) of the frozen/thawed spermatozoa.     

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis,Immaturity and Oxidative Stress

Sperm DNA fragmentation (sDF) represents a threat to male fertility, human reproduction and the health of the offspring. The causes of sDF are still unclear, even if apoptosis, oxidative assault and defects in chromatin maturation are hypothesized. Using multicolor flow cytometry and sperm sorting, we challenged the three hypothesized mechanisms by simultaneously evaluating sDF and signs of oxidative damage (8-hydroxy, 2′-deoxyguanosine [8-OHdG] and malondialdehyde [MDA]), apoptosis (caspase activity and cleaved poly[ADP-ribose] polymerase [cPARP]) and sperm immaturity (creatine phosphokinase [CK] and excess of residual histones). Active caspases and c-PARP were concomitant with sDF in a high percentage of spermatozoa (82.6% ± 9.1% and 53.5% ± 16.4%, respectively). Excess of residual histones was significantly higher in DNA-fragmented sperm versus sperm without DNA fragmentation (74.8% ± 17.5% and 37.3% ± 16.6%, respectively, p < 0.005), and largely concomitant with active caspases. Conversely, oxidative damage was scarcely concomitant with sDF in the total sperm population, at variance with live sperm, where 8-OHdG and MDA were clearly associated to sDF. In addition, most live cells with active caspase also showed 8-OHdG, suggesting activation of apoptotic pathways in oxidative-injured live cells. This is the first investigation on the origin of sDF directly evaluating the simultaneous presence of the signs of the hypothesized mechanisms with DNA breaks at the single cell level. The results indicate that the main pathway leading to sperm DNA breaks is a process of apoptosis, likely triggered by an impairment of chromatin maturation in the testis and by oxidative stress during the transit in the male genital tract. These findings are highly relevant for clinical studies on the effects of drugs on sDF and oxidative stress in infertile men and for the development of new therapeutic strategies.     

Chromosomal Abnormality and Y Chromosome Microdeletion in Chinese Patients with Azoospermia or Severe Oligozoo-spermia

Chromosomal abnormality and Y chromosome microdeletion are regarded as two frequent genetic causes associated with spermatogenic failure in Caucasian population. To investigate the distribution of the two genetic defects in Chinese patients with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 358 idiopathic infertile men, including 256 patients with azoospermia and 102 patients with severe oligozoospermia, and screening of AZF region microdeletion of Y chromosome by multiplex PCR was performed in those patients without detectable chromosomal abnormality and 100 fertile controls. Of 358 patients, 39(10.9%) were found to have chromosomal abnormalities in which Klinefelters syndrome (47, XXY) was the most common chromosomal aberration. The incidence of sex chromosomal abnormality in patients with azoospermia was significantly higher than that in patients with severe oligozoospermia (12.1% vs 1%). Among the rest of the 319 patients with normal karyotype, 46 (14.4%) were found to have microdeletions in AZF region. The prevalence rates of AZF microdeletion was 15% and 13.1% in patients with azoospermia and severe oligozoospermia respectively. The microdeletion in AZFc was the most frequent deletion and all the microdeletions in AZFa were found in azoospermic patients. No microdeletion in AZF region was detected in fertile controls. In conclusion, chromosomal abnormality and AZF region microdeletion of Y chromosome might account for about 25% of Chinese infertile patients with azoospermia or severe oligozoospermia, suggesting the two abnormalities are important genetic etiology of spematogenic failure in Chinese population and it is essential to screen them during diagnosis of male infertility before in vitro assisted fertilization by introcytoplasmic sperm injection.     

Imidazole-induced cell death,associated with intracellular acidification,caspase-3 activation,DFF-45 cleavage,but not oligonucleosomal DNA fragmentation

Intracellular acidification is known to be involved in the initiation phase of apoptosis. However, the necessity of intracellular acidic conditions in the execution phase of apoptosis remains unknown. In this study, we found that in HL-60 cells imidazole induces cell death, associated with intracellular acidification, caspase-3 activation and DFF-45 cleavage, but not oligonucleosomal DNA fragmentation. A caspase inhibitor prevented cell death but not intracellular acidification. When pHi was neutralized by changing from imidazole-containing medium to fresh medium, oligonucleosomal DNA fragmentation and increased caspase-3 activity was observed in the imidazole-treated HL-60 cells. Furthermore, the DNA fragmentation induced by intracellular neutralization was inhibited by caspase inhibitor treatment. These results indicate that imidazole induces caspase-dependent cell death, and suggest that maintaining pHi in the neutral range is essential for the induction of oligonucleosomal DNA fragmentation in the execution phase of apoptosis.     

Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction

Male infertility is a multi‐factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non‐azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males. Mol. Reprod. Dev. 79: 637–650, 2012. © 2012 Wiley Periodicals, Inc.     

SNPs in KIT and KITLG genes may be associated with oligospermia in Chinese population

Abstract

KIT/KITLG signaling system is crucial for spermatogenesis, which suggests that KIT and KITLG genes may be involved in spermatogenesis impairment and male infertility. To explore the possible association of KIT and KITLG genes with male infertility having spermatogenesis impairment, polymorphism distributions of SNP rs3819392 in KIT gene as well as rs995030 and rs4474514 in KITLG gene were investigated in 372 patients with idiopathic azoospermia or oligospermia and 205 fertile controls. As a result, the significant differences in polymorphism distributions of SNP rs3819392 in KIT gene and rs4474514 in KITLG gene were observed between the patients with oligospermia and controls. The frequencies of allele G (94.2% versus 90.0% p?=?0.022) and genotype GG (89.2% versus 82.0% p?=?0.042) in patients with oligospermia were significantly higher than those in controls at rs3819392 locus in KIT gene. In addition, the genotype CC of rs4474514 in KITLG (8.2% versus 3.4%, p?=?0.034) also significantly increased in oligospermic patients in comparison to controls. These findings indicated that SNP rs3819392 in KIT gene and rs4474514 in KITLG gene may be associated with oligospermia, suggesting that polymorphism of KIT and KITLG genes may play a role in oligospermia.     

Significance of the caspase family in Helicobacter pylori induced gastric epithelial apoptosis

Background and Aims. H. pylori infection results in an increased epithelial apoptosis in gastritis and duodenal ulcer patients. We investigated the role and type of activation of caspases in H. pylori‐induced apoptosis in gastric epithelial cells. Methods. Differentiated human gastric cancer cells (AGS) and human gastric mucous cell primary cultures were incubated with H. pylori for 0.5–24 hours in RPMI 1640 medium, and the effects on cell viability, epithelial apoptosis, and activity of caspases were monitored. Apoptosis was analyzed by detection of DNA‐fragments by Hoechst stain®, DNA‐laddering, and Histone‐ELISA. Activities of caspases were determined in fluorogenic assays and by Western blotting. Cleavage of BID and release of cytochrome c were analyzed by Western blot. Significance of caspase activation was investigated by preincubation of gastric epithelial cells with cell permeable specific caspase inhibitors. Results. Incubation of gastric epithelial cells with H. pylori caused a time and concentration dependent induction of DNA fragmentation (3‐fold increase), cleavage of BID, release of cytochrome c and a concomittant sequential activation of caspase‐9 (4‐fold), caspase‐8 (2‐fold), caspase‐6 (2‐fold), and caspase‐3 (6‐fold). No effects on caspase‐1 and ‐7 were observed. Activation of caspases preceded the induction of DNA fragmentation. Apoptosis could be inhibited by prior incubation with the inhibitors of caspase‐3, ‐8, and ‐9, but not with that of caspase‐1. Conclusions. Activation of certain caspases and activation of the mitochondrial apoptotic pathway are essential for H. pylori induced apoptosis in gastric epithelial cells.     

Caspase 3 inhibition attenuates hydrogen peroxide-induced DNA fragmentation but not cell death in neuronal PC12 cells

Exposure of neurons to H(2)O(2) results in both necrosis and apoptosis. Caspases play a pivotal role in apoptosis, but exactly how they are involved in H(2)O(2)-mediated cell death is unknown. We examined H(2)O(2)-induced toxicity in neuronal PC12 cells and the effects of inducible overexpression of the H(2)O(2)-scavenging enzyme catalase on this process. H(2)O(2) caused cell death in a time- and concentration-dependent manner. Cell death induced by H(2)O(2) was found to be mediated in part through an apoptotic pathway as H(2)O(2)-treated cells exhibited cell shrinkage, nuclear condensation and marked DNA fragmentation. H(2)O(2) also triggered activation of caspase 3. Genetic up-regulation of catalase not only significantly reduced cell death but also suppressed caspase 3 activity and DNA fragmentation. While the caspase 3 inhibitor DEVD inhibited both caspase 3 activity and DNA fragmentation induced by H(2)O(2) it did not prevent cell death. Treatment with the general caspase inhibitor ZVAD, however, resulted in complete attenuation of H(2)O(2)-mediated cellular toxicity. These results suggest that DNA fragmentation induced by H(2)O(2) is attributable to caspase 3 activation and that H(2)O(2) may be critical for signaling leading to apoptosis. However, unlike inducibly increased catalase expression and general caspase inhibition both of which protect cells from cytotoxicity, caspase 3 inhibition alone did not improve cell survival suggesting that prevention of DNA fragmentation is insufficient to prevent H(2)O(2)-mediated cell death.     

Quercetin protects HCT116 cells from Dichlorvos-induced oxidative stress and apoptosis

The present study was designed to assess the possible protective effects of Quercetin (QUER), a flavonoid with well-known pharmacological effects, against Dichlorvos (DDVP)-induced toxicity in vitro using HCT116 cells. The cytotoxicity was monitored by cell viability, reactive oxygen species (ROS) generation, anti-oxidant enzyme activities, malondialdehyde (MDA) production, and DNA fragmentation. The apoptosis was assessed through the measurement of the mitochondrial transmembrane potential (ΔΨm) and caspase activation. The results indicated that pretreatment of HCT116 cells with QUER, 2 h prior to DDVP exposure, significantly decreased the DDVP-induced cell death, inhibited the ROS generation, modulated the activities of catalase (CAT) and superoxide dismutase (SOD), and reduced the MDA level. The reductions in mitochondrial membrane potential, DNA fragmentation, and caspase activation were also attenuated by QUER. These findings suggest that dietary QUER can protect HCT116 cells against DDVP-induced oxidative stress and apoptosis.     

L’Inhibine B sérique, marqueur sensible de la production spermatique chez l’homme

Several recent papers indicate that the blood concentration of inhibin B measured by the dimeric assay is a marker of human spermatogenesis. The aim of the present study was to validate the dimeric assay in our hospital. For this purpose, we studied a population of 106 patients attending our infertility clinic. We found that serum inhibin B levels were positively correlated with the level of sperm production as reflected by the sperm concentration and negatively correlated with serum FSH levels. Serum inhibin B concentrations were found to be superior to FSH levels for discriminating between subgroups of patients with different levels of sperm production. For example, the differences in the inhibin B levels in severe oligozoospermia (< 5×106 sperm/ml) compared to non-obstructive azoospermia were more pronounced than the differences in FSH (p=0.0002 vs p=0.007, respectively). Overall, the results obtained in the present study were similar to those reported in other studies based on the same assay. Serum inhibin B levels in patients with non obstructive azoospermia were ten times lower than in patients with normal sperm concentrations. From a practical point of view, the measurement of serum inhibin B opens up new possibilities for the diagnosis and prognosis of many testicular disorders. Firstly, serum inhibin B determination should be performed whenever reproductive hormones are prescribed. In the particular case of azoospermia, serum inhibin B concentrations appear to be particularly useful to distinguish between obstructive and non-obstructive situations. Finally, according to a recent publication, a serum inhibin B cut-off value (> 40 pg/mL) could predict the success of testicular sperm extraction in patients with non-obstructive azoospermia. Serum inhibin B could therefore represent a unique non-invasive marker of focal hypospermatogenesis in men with non-obstructive azoospermia, who are candidates for intracytoplasmic sperm injection (ICSI) and a useful early marker to monitor possible recovery of spermatogenesis after chemotherapy or radiotherapy.     

Relationship of SNP of H2BFWT gene to male infertility in a Chinese population with idiopathic spermatogenesis impairment

The H2B family, member W, testis specific (H2BFWT) gene encodes a testis specific histone that plays a crucial role in reorganization and remodeling of chromatin and epigenetic regulation during spermatogenesis, suggesting that the gene may be involved in spermatogenesis impairment. To test the speculation, the allele and haplotype frequencies of two single-nucleotide polymorphism loci in this gene, -9C>T and 368A>G, were investigated in 409 infertile patients with idiopathic azoospermia or oligozoospermia and 209 fertile men as controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. As the results, the frequencies of -9T (52.8% vs. 41.6%, p = 0.009) and 368G (43.0% vs. 32.5%, p = 0.012) were significantly higher in patients than those in controls; after stratifying patients, the significant higher frequencies were still detected in allele -9T for azoospermia (57.4% vs. 41.6%, p = 0.001) and allele 368G for oligozoospermia (45.4% vs. 32.5%, p = 0.007). The haplotype CA was significantly decreased (22.8% vs. 33.0%, p = 0.006) whereas TG was significantly increased (18.3% vs. 7.2%, p < 0.001) in infertile patients compared with controls. These results indicated that the polymorphism -9C>T and 368A>G in H2BFWT gene are associated with male infertility with idiopathic azoospermia or oligozoospermia, suggesting that H2BFWT gene might be contribute to susceptibility to spermatogenesis impairment in Chinese population.     

Selenium status of idiopathic infertile Nigerian males

Selenium concentration in the sera and seminal plasma of 60 infertile males (40 oligospermia and 20 azoospermia) and 40 males with proven evidence of fertility (normospermia; control group) were estimated using atomic absorption spectrophotometry. Results were correlated with spermatogram and hormonal levels in order to determine their relationship and significance in male infertility. The mean serum concentrations of selenium was found to be significantly increased in oligospermic compared to azoospermic subjects and controls (p<0.01), whereas the seminal plasma level was significantly higher in azoospermic compared to oligospermic subjects and controls (p<0.001). Thus, the ratio of serum selenium to seminal plasma selenium was 1∶1 in controls, 4∶1 in oligospermia, and 1∶2 in azoospermic subject. A significant inverse correlation was observed between serum selenium level and sperm count (p<0.01). Similarly, seminal plasma selenium correlated with spermatozoa motility, viability, and morphology. Serum selenium level shows positive correlation with the serum testosterone level (p<0.01). In conclusion, there appears to be a physiological balance in the distribution of selenium in serum and seminal plasma compartment of control males. A disturbance in this balance has a significant influence on spermatogenesis. Selenium appears to have a positive influence on Leydig cells, thus influencing the secretion of testosterone.