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.     

中国无精症、严重寡精症患者的染色体异常和Y染色体微缺失

染色体异常和Y染色体微缺失被认为是两个白种人群中常见的生精障碍相关遗传因素。为了解中国无精症、严重寡精症患者中的染色体异常和Y染色体微缺失,运用染色体G显带技术,在358个原发无精症（256人）和严重寡精症（102人）不育患者中进行染色体核型分析;同时运用多重PCR技术,在核型正常的患者和100个正常生育男性中,对Y染色体AZF区微缺失进行筛查。在358个患者中,39人（10．9％）发现有染色体异常,Klinefelter（47,XYY）最为常见。无精症患者性染色体异常频率明显高于严重寡精症患者（12．1％VS1％）。在319个核型正常的患者中,46（14．4％）发现有AZF区微缺失,无精症和寡精症患者中Y染色体微缺失频率分别为15％和13．1％,AZFc区的微缺失最为常见,AZFa区的微缺失只见于无精症患者,正常生育男性中未发现AZF区的微缺失。结果显示,在中国无精症、严重寡精症患者中,大约25％的患者有染色体异常或Y染色体AZF区微缺失,提示这两种遗传异常是中国人群生精障碍的重要相关遗传病因,有必要在男性不育的诊断以及利用细胞浆内精子注射技术进行辅助生育时,对患者的这些遗传异常进行筛查。     

Chromosomal evaluation in a group of Tunisian patients with non-obstructive azoospermia and severe oligozoospermia attending a Tunisian cytogenetic department

Male infertility is the cause in half of all childless partnerships. Numerous factors contribute to male infertility, including chromosomal aberrations and gene defects. Few data exist regarding the association of these chromosomal aberrations with male infertility in Arab and North African populations. We therefore aimed to evaluate the frequency of chromosomal aberrations in a sample of 476 infertile men with non-obstructive azoospermia (n = 328) or severe oligozoospermia (n = 148) referred for routine cytogenetic analysis to the department of cytogenetics of the Pasteur Institute of Tunis. The overall incidence of chromosomal abnormalities was about 10.9%. Out of the 52 patients with abnormal cytogenetic findings, sex chromosome abnormalities were observed in 42 (80.7%) including Klinefelter syndrome in 37 (71%). Structural chromosome abnormalities involving autosomes (19.2%) and sex chromosomes were detected in 11 infertile men. Abnormal findings were more prevalent in the azoospermia group (14.02%) than in the severe oligozoospermia group (4.05%). The high frequency of chromosomal alterations in our series highlights the need for efficient genetic testing in infertile men, as results may help to determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations.     

AZF microdeletions on the Y chromosome of infertile men from Turkey

Intervals V and VI of Yq11.23 regions contain responsible genes for spermatogenesis, and are named as "azoospermia factor locus" (AZF). Deletions in these genes are thought to be pathogenetically involved in some cases of male infertility associated with azoospermia or oligozoospermia. The aim of this study was to establish the prevalence of microdeletions on the Y chromosome in infertile Turkish males with azoospermia or oligozoospermia. We applied multiplex polymerase chain reaction (PCR) using several sequence-tagged site (STS) primer sets, in order to determine Y chromosome microdeletions. In this study, 61 infertile males were enrolled for the molecular AZF screening program. In this cohort, one infertile male had 46,XX karyotype and the remaining had 46,XY karyotypes. Forty-eight patients had a diagnosis of azoospermia and 13 had oligozoospermia. Microdeletions in AZFa, AZFb and AZFc (DAZ gene) regions were detected in two of the 60 (3.3%) idiopathic infertile males with normal karyotypes and a SRY translocation was determined on 46,XX male. Our findings suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.     

无精子症和严重少精子症患者Y染色体微缺失研究

目的：研究Y染色体微缺失与男性不育的关系。方法：采用多重PCR技术,研究正常男性、无精子症和严重少精子症男性不育患者Y染色体无精子因子（AZF）区域3个序列标志位点（STS）的缺失情况。结果：在93例无精子症或严重少精子症患者中,15例有Y染色体微缺失,缺失率为16%。其中,42例无精子症患者中,6例为AZFc区SY255位点缺失,2例为AZFb区SY134位点缺失;51例严重少精子症患者中,7例为AZFc区SY255位点缺失。40例正常男性无Y染色体微缺失。结论：多重PCR技术是简便而有效的对男性不育患者进行Y染色体微缺失筛查的方法;Y染色体微缺失是造成男性不育的一个重要原因,对男性不育患者进行辅助生育技术治疗前应常规进行Y染色体微缺失的检测。     

Molecular analysis of Y chromosome microdeletions in idiopathic cases of male infertility in Serbia

The aim of this study was to detect frequency of microdeletions of Y chromosome in idiopathic cases of male infertility in Serbian population. Patients were subjected to detailed clinical, endocrinological and cytogenetic examinations. Ninety patients with normal cytogenetic findings with azoospermia and severe oligozoospermia were included in the study. In these patients microdeletion analysis was performed by multiplex polymerase chain reaction (PCR) method on DNA extracted from peripheral blood. In each case 6 markers in azoospermia factor (AZF) regions were tested: sY84, sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc). Deletions on Y chromosome were detected in 14 of 90 cases (15.6%), 9 with azoospermia and 5 with severe oligozoospermia. Of total number of 17 deletions, 11 (64.7%) were detected in AZFc region, 3 (17.6%) in AZFa region and 3 (17.6%) in AZFb region. Microdeletions in AZF region of Y chromosome, especially AZFc microdeletions, represent common genetic cause of idiopathic azoospermia and severe oligozoospremia in Serbian infertile men. Therefore, testing for Y chromosome microdeletions should be considered as an important element in diagnosis and genetic counseling of infertile men in Serbia and decisions regarding the assisted reproduction should be made based on the presence and type of AZF microdeletions.     

Chromosome abnormalities in sperm from infertile men with normal somatic karyotypes: oligozoospermia

Recently, intracytoplasmic sperm injection (ICSI) has been extremely successful for the treatment of male infertility. However, transmission of cytogenetic defects to offspring is a great concern. There are two types of cytogenetic problems in patients seeking ICSI; one is the transmission of genetic defects from patients with constitutional chromosomal abnormalities and the second is the generation of de novo defects in infertile men. Generally about 5.1% of infertile men have chromosomal abnormalities. Among such infertile men, men with severe spermatogenesis defects, including oligozoospermia and azoospermia, are subjects for ICSI. Therefore it is very important to obtain cytogenetic information in these infertile patients. Furthermore, oligozoospermic men with a normal somatic karyotype also have increased frequencies of sperm chromosome abnormalities. Oligozoospermia is usually associated with other sperm alterations, for example oligoasthenozoospermia, oligoteratozoospemia and oligoasthenoteratozoospermia. In this review, the relationship between sperm concentration and sperm aneuploidy frequencies has been analyzed. The inverse correlation between the frequency of sperm aneuploidy and concentration has been reported in extensive studies. Especially in severe oligozoospermia, a significantly higher frequency of sex chromosome aneuploidy has been observed and this has been corroborated in recent clinical outcome data of ICSI.     

Molecular analysis of Y chromosome microdeletions in idiopathic cases of male infertility in Serbia

The aim of this study was to detect frequency of microdeletions of Y chromosome in idiopathic cases of male infertility in Serbian population. Patients were subjected to detailed clinical, endocrinological and cytogenetic examinations. Ninety patients with normal cytogenetic findings with azoospermia and severe oligozoospermia were included in the study. In these patients microdeletion analysis was performed by multiplex polymerase chain reaction (PCR) method on DNA extracted from peripheral blood. In each case 6 markers in azoospermia factor (AZF) regions were tested: sY84, sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc). Deletions on the Y chromosome were detected in 14 of 90 cases (15.6%), nine with azoospermia and five with severe oligozoospermia. Of total number of 17 deletions, 11 (64.7%) were detected in AZFc region, three (17.6%) in AZFa region and three (17.6%) in AZFb region. Microdeletions in AZF region of the Y chromosome, especially AZFc microdeletions, represent common genetic cause of idiopathic azoospermia and severe oligozoospremia in Serbian infertile men. Therefore, testing for Y chromosome microdeletions should be considered as an important element in diagnosis and genetic counseling of infertile men in Serbia and decisions regarding the assisted reproduction should be made based on the presence and type of AZF microdeletions. The text was submitted by the authors in English.     

Impact de la varicocélectomie chez les patients ayant une azoospermie non obstructive ou une oligozoospermie sévère

Objective

To evaluate the changes induced by retroperitoneal varicocelectomy on infertile men with nonobstructive azoospermia or severe oligozoospermia.

Patients and methods

The records were retrospectively evaluated for 46 infertile men with severe oligozoospermia (group I) and 15 infertile men with non-obstructive azoospermia (group II). The parameters of sperm before and after surgery and unassisted pregnancy rate were comparatively analysed.

Results

In the severe oligozoospermia group, the mean age of patients was 35.5 ± 6.4 (23–47 years). The mean duration of infertility was 4.9 ± 3.4 years (1–13 years). Of these patients, 41(89.1%) had bilateral varicocele and five (10.9%) had unilateral left-side varicocele. The varicocele was classified as grade I in two cases (4.3%), grade II in 39 cases (84.7%) and grade III in five cases (10.9%). After surgery, the mean sperm count increased from 1.85 ± 1.4 to 8.3 ± 10.3 millions/ml and mean sperm normal motility from 43.3 ± 21.5 to 47.6 ± 29.2%. The mean sperm abnormal morphology decreased from 65.05 ± 21.6 to 50.08 ± 26.9%. After a mean follow-up of 26.2 ± 11.6 months, the unassisted pregnancy rate in this group was 26.1%. In the non-obstructive azoospermia group (N = 15), the mean age of patients was 40.8 ± 7.2 (27–47 years). The mean duration of infertility was 6 ± 3.1 years (3–15 years). After varicocelectomy, an induction of spermatogenesis was observed in three patients (20%) with presence of motile sperm in the ejaculate. In this group, only one of the 15 men achieved unassisted pregnancy.

Conclusion

Retroperitoneal varicocele repair resulted in spermatogenesis induction with presence of motile ejaculated spermatozoa for some men with non-obstructive azoospermia. It induced spermatogenesis and fertility enhancement in men with severe oligozoospermia. Varicocele repair should be considered in men with non-obstructive azoospermia or severe oligozoospermia.     

Y chromosome micro-deletions in idiopathic infertility from Northern India

Azoospermia factor locus (AZF) is assumed to contain the genes responsible for spermatogenesis. Deletions in these genes are thought to be pathologically involved in some cases of male infertility associated with azoospermia or oligozoospermia. An attempt was made to establish the prevalence of micro-deletions on the Y chromosome in 79 infertile North Indians with azoospermia and oligozoospermia. Detail clinical examinations as well as endocrinological parameters were also done. Polymerase chain reaction (PCR) micro-deletion analysis was done in 79 infertile men. For this, genomic DNA was extracted from the peripheral blood. Seven sets of primers were used encompassing AZFa, AZFb and AZFc regions. Micro-deletions in five of the 79 cases (6.3%) showed deletions of at least one of the STS markers. Deletions were detected with known and unknown aetiology and at least in one of the infertile male with varicocele. AZF micro-deletions seen in idiopathic infertile males suggest the need for molecular screening in non-idiopathic cases.     

Screening for microdeletions in human Y chromosome--AZF candidate genes and male infertility

About 30% of couple infertilities are of male origin, some of them caused by genetic abnormalities of the Y chromosome. Deletions in AZF region can cause severe spermatogenic defects ranging from non-obstructive azoospermia to oligospermia. The intracytoplasmatic sperm injection technique (ICSI) is rapidly becoming a versatile procedure for human assisted reproduction in case of male infertility. The use of ICSI allows Y chromosome defects to be passed from father. The goal of our study is to evaluate the frequency of microdeletions in the long arm of Y chromosome, within the AZF regions, in these cases of infertilities, using molecular genetics techniques. Thirty infertile men with azoospermia or oligozoospermia, determined by spermogram, were studied after exclusion of patients with endocrine or obstructive causes of infertility. Peripheral blood DNA was extracted from each patient, then amplified by multiplex PCR with STS genomic markers from the Y chromosome AZF zones. Each case was checked by multiplex PCR through coamplification with the SRY marker. Three men with microdeletions of the long arm of the Y chromosome were diagnosed among the 30 patients, corresponding to a proportion of 10%. The relatively high proportion of microdeletions found in our population suggest the need for strict patient selection to avoid unnecessary screening for long arm Y chromosome microdeletions. The molecular diagnostics was performed according to the current European Academy of Andrology laboratory guidelines for molecular diagnosis of Y chromosomal microdeletions.     

A comparison of the frequency of sperm chromosome abnormalities in men with mild,moderate, and severe oligozoospermia

Infertile men undergoing intracytoplasmic sperm injection have an increased frequency of chromosome abnormalities in their sperm. Men with low sperm concentration (oligozoospermia) have an increased risk of sperm chromosome abnormalities. This study was initiated to determine whether men with severe oligozoospermia (<10(6) sperm/ml) have a higher frequency of chromosome abnormalities in their sperm compared with men with moderate (1-9 x 10(6) sperm/ml) or mild (10-19 x 10(6) sperm/ml) oligozoospermia. Multicolor fluorescence in situ hybridization analysis was performed using DNA probes specific for chromosomes 13, 21, X, and Y (with chromosome 1 as an autosomal control for the sex chromosomes). Aneuploidy and disomy frequencies were assessed from a total of 603,011 sperm from 30 men: 10 in each of the categories. The mean frequencies of disomy for the patients with mild, moderate, and severe oligozoospermia were 0.17%, 0.24%, and 0.30%, respectively, for chromosome 13 and 0.22%, 0.44%, and 0.58%, respectively, for chromosome 21. For the sex chromosomes, the mean frequencies of disomy for mild, moderate, and severe oligozoospermia were 0.25%, 1.04%, and 0.68%, respectively, for XY, 0.047%, 0.08%, and 0.10%, respectively, for XX, and 0.04%, 0.06%, and 0.09%, respectively, for YY. The frequencies for diploidy also increased from 0.4% for mild to 1.20% for moderate to 1.24% for severe oligozoospermia. There was a significant inverse correlation between the frequency of sperm chromosome abnormalities and the sperm concentration for XY, XX, and YY disomy and diploidy. These results demonstrate that men with severe oligozoospermia have an elevated risk for chromosome abnormalities in their sperm, particularly sex chromosome abnormalities.     

Types of Y chromosome deletions and their frequency in infertile men

Deletions of Y chromosome AZF locus were analyzed during a large-scale andrological and genetic examination of 810 infertile men. The search for Yq microdeletions was carried out according to the standard EAA/EMQN guidelines. The breakpoints were mapped for the deletions in AZF locus. The Y chromosome macro- and microdeletions were detected in 61 (7.5%) infertile men. The frequencies of AZF deletions during azoospermia and severe oligozoospermia amounted to 12.2 and 8.1 %, respectively. On the whole, the frequencies of Yq microdeletions and the genophenotypic correlations characteristic of various AZF deletion types comply with the relevant published data. However, spermatozoids in the ejaculate sediment of men with completely deleted AZFa region or AZFb+c deletions (from solitary spermatozoids to several dozens) were detected for the first time. It was demonstrated that the breakpoints were localized between AZFa and AZFb regions proximally to AZFb+c microdeletions for the majority of cytogenetically detectable deletions in the Y chromosome long arm. This indicates that the mechanisms underlying Yq macro- and microdeletions are somewhat different. The issues related to the role of Y chromosome deletions in the origins of monosomy for X chromosome and X/XY mosaicism are discussed.     

Cytogenetic and molecular analysis of male infertility

Reduced male fertility and subfertility can be caused by genetic factors that affect both germ cell development, differentiation, and function; in particular, chromosome abnormalities and Yq microdeletions are a possible cause of spermatogenetic impairment in males as shown by their higher frequency in infertile men than in the general male population. Microdeletion of the long arm of the Y chromosome (Yq) are associated with spermatogenic failure and have been used to define three regions on Yq (AZFa, AZFb, and AZFc) that are critical for germ cell development. With the advent of assisted reproductive technology and intracytoplasmic sperm injection, knowledge about the various factors leading to spermatogenic impairment is one of the most important aspects of scientific research. Therefore, this study was designed to identify the frequency of cytogenetic and submicroscopic interstitial deletions in azoospermia factor loci in infertile Indian males. One hundred and eighty males with nonobstructive oligozoospermia and azoospermia were included in this study. Semen analysis was done in each case to determine the spermatogenic status. Individuals were subjected to detailed clinical examination, family history, and endocrinological and cytogenetic study after consent from the patient. Peripheral blood cultures were set up according to standard protocols and 30 G-banded metaphases were analyzed in each case. Numerical and structural chromosomal abnormalities were detected in 40 infertile cases. Fluorescence in situ hybridization analysis was done in some cases to identify the percentage of mosaic cell lines and any cryptic or low-level mosaicism. Polymerase chain reaction microdeletion analysis was done in 140 cytogenetically normal cases. Of the 140 cases, 8 showed deletion of at least one of the sequence-tagged site markers. Review of literature has shown that the overall frequency of microdeletions varies from 1 to 55%. In the present study, the frequency of microdeletion was 5.8%, and deletions were identified in cases with undescended testis and varicocele and cases with bilateral severe testiculopathy.     

Types of Y chromosome deletions and their frequency in infertile men

Y chromosome deletions in the AZF locus were analyzed during a large-scale andrological and genetic examination of 810 infertile men. The search for Yq microdeletions was carried out according to the standard EAA/EMQN guidelines. The breakpoints were mapped for the revealed AZF deletions. The Y chromosome macro-and microdeletions were detected in 61 (7.5%) infertile men. The frequencies of AZF deletions in patients with azoospermia and severe oligozoospermia amounted to 12.2 and 8.1%, respectively. On the whole, the frequencies of Yq microdeletions and the genophenotypic correlations characteristic of various AZF deletion types agree with the relevant published data. However, spermatozoa in the ejaculate sediment of men with completely deleted AZFa region or AZFb+c deletions (from solitary spermatozoa to several dozens) were detected for the first time. It was demonstrated that the breakpoints were localized between AZFa and AZFb regions proximally to AZFb+c microdeletions for the majority of cytogenetically detectable deletions of the Y chromosome long arm. This indicates that the mechanisms underlying Yq macro-and microdeletions are somewhat different. The issues related to the role of Y chromosome deletions in the origins of X chromosome monosomy and X/XY mosaicism are discussed.     

Is there a relationship between sperm chromosome abnormalities and sperm morphology?

This review explores the relationship between sperm chromosomal constitution and morphology. With the advent of techniques for obtaining information on the chromosome complements of spermatozoa, this relationship has been studied in fertile men and in men with a high frequency of chromosomal abnormalities. Using human sperm karyotype analysis, no relationship between sperm chromosome abnormalities and morphology was found in fertile men, translocation carriers or post-radiotherapy cancer patients. Fluorescence in situ hybridization (FISH) analysis has not generally revealed a specific association between morphologically abnormal sperm and sperm chromosome abnormalities, but has indicated that teratozoospermia, like other forms of abnormal semen profiles (aesthenozoospermia, oligozoospermia) is associated with a modest increase in the frequency of sperm chromosome abnormalities. However, FISH studies on some infertile men and mouse strains have suggested that certain types of morphologically abnormal spermatozoa, such as macrocephalic multitailed spermatozoa, are associated with a very significantly increased frequency of aneuploidy. Thus, there may be an association between sperm morphology and aneuploidy in infertile men with specific abnormalities.     

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.     

Emulsion PCR-based method to detect Y chromosome microdeletions

Deletions in Y chromosome are thought to be pathologically involved in some cases of male infertility associated with azoospermia or oligozoospermia. An emulsion-based multiplex PCR method was developed for detecting Y chromosome microdeletions in infertile men and a plasma sample of pregnant women carrying a male fetus. The sensitivity of multiplex PCR in emulsion was evaluated. Conventional PCR was also carried out for comparison. A total of 13 sequence-tagged sites (STSs) distributed in the AZF region were analyzed simultaneously with this method. The SRY gene was also detected as the inner control. Results showed that Y chromosome microdeletions were found in 4 of 19 infertile patients. Also, in 1 of 63 samples collected from pregnant women, microdeletions were found in some of the detected sites. It is suggested that the emulsion PCR assay was proven to be a promising diagnostic tool and could be widely used in further clinical and academic research.     

Association of prostate cancer susceptibility variant (MSMB) rs10993994 with risk of spermatogenic failure

β-Microseminoprotein (MSMB) is one of the most abundant proteins in human seminal plasma. It has been identified that MSMB increased significantly in oligoasthenoteratozoospermic patients compared with fertile controls. We hypothesized that the functional polymorphism (rs10993994) of MSMB gene could be a risk factor for spermatogenic failure. For this study, 338 patients with idiopathic oligozoospermia or azoospermia and 382 fertile controls were recruited from an infertility clinic. Semen analysis was performed by computer-assisted semen analysis system. The functional polymorphism of MSMB gene was genotyped using TaqMan method. Sixty three seminal plasma samples were used to test the expression of MSMB by enzyme-linked immunosorbent assay (ELISA). The TT genotype and T allele were associated with an increased risk of idiopathic infertility with azoospermia (TT genotype: OR, 1.75; 95% CI, 1.03–2.95; T allele: OR, 1.34; 95% CI, 1.03–1.75). However, no differences were found in risk for the TT genotype or T allele among men with oligozoospermia. In addition, idiopathic infertile males have significantly higher MSMB expression levels than fertile controls. We present the first epidemiologic evidence supporting the involvement of common genetic polymorphism in MSMB gene in spermatogenic failure. These results suggest that men carrying the variant have an increased risk of spermatogenic failure associated with male infertility. Further studies are needed to confirm the roles of the polymorphism in idiopathic azoospermia and investigate the biological mechanism of elevated MSMB expression in infertile males.     

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.