Tracking microdeletions of the AZF region in a patrilineal line of infertile men

Male infertility is considered to be a difficult-to-treat condition because it is not a single entity, but rather reflects a variety of different pathologic conditions, thus making it difficult to use a single treatment strategy. Structural alterations in the Y chromosome have been the principal factor responsible for male infertility. We examined 26 family members of 13 patients with male infertility who showed deletions in the AZF region. In family 1, the father and a brother did not show microdeletions. However, a son showed a microdeletion in AZFa (sY84) and an azoospermic sperm analysis, but another son had a microdeletion in AZFa (sY84) and AZFb (sY127) and a normal sperm analysis. The father of family 2, with severe oligozoospermia, had a microdeletion in the AZFa region (sY84) and his son, conceived by intracytoplasmic sperm injection, also showed the same microdeletion. In the other families, only the men with an altered sperm analysis had a microdeletion. It is possible that in family 1, the father and brother who did not show microdeletions in this study, could have microdeletions in regions upstream or downstream of the one analyzed. The treatment with intracytoplasmic sperm injection can result in vertical transmission of microdeletions of the AZF region and can also cause the expansion of a de novo mutation. This finding reinforces the necessity of an investigation of microdeletions of the Y chromosome in individuals who are candidates for assisted reproduction, as well as genetic counciling and follow-up.     

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.     

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。     

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.     

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.     

对法医学相关的DYS549、DYS527和DYS459基因座在男性不育症人群中的缺失、重复调查

位于Y染色体无精症因子区域(Azoospermia factor, AZF)的基因座位点DYS549、DYS527和DYS459在法医学鉴定和家系分析中被广泛应用。但是,在男性不育患者中,DYS549、DYS527和DYS459位点很可能会表现出特殊的基因型,对应用Y染色体短串联重复序列(Y chromosome short tandem repeat, Y-STR)进行个体识别的结果产生干扰。因此,文章应用14个Y-STR基因座复合扩增体系和Y染色体AZFc区DAZ、CDY1基因的拷贝数检测等方法,探讨男性不育症中法医学相关的3个Y-STR基因座的异常分型,对个体识别和家系分析中的DNA检验异常结果提供合理的解释。在240例男性非梗阻性无精、严重少精、先天性双侧输精管缺如(CBVAD)患者中,采用改良的多重PCR体系进行AZF区域微缺失的序列标签位点(Sequence tagged sites, STSs)检测,发现AZF微缺失40例(AZFa：2例;AZFb：2例;AZFc：30例;AZFb+c：6例),AZF的总缺失率为16.67%。应用14 Y-STR复合扩增体系对上述AZF微缺失的阳性患者样本进行检测,发现所有AZFb缺失患者存在DYS549等位基因缺失,AZFc缺失患者存在DYS527、DYS459等位基因缺失,AZFb+c缺失患者存在DYS549、DYS527和DYS459等位基因缺失。在AZF微缺失阴性的不育症患者中,通过检测DAZ、CDY1基因拷贝数发现10例AZFc部分复制的患者(1例为先天性输精管缺如,2例非梗阻性无精症,7例严重少精子症),占所调查不育人群的4.17%。男性不育人群AZF区域3个Y-STR基因座多态性会造成等位基因缺失或者重复,这些异常分型是由于临床遗传缺陷造成的而不是实验偏差。阐明Y-STR在男性不育人群中的异质性可以更好地完善Y-STR数据库和解释STR实验结果。     

A cost-effective screening test for detecting AZF microdeletions on the human Y chromosome

PCR-based screening of microdeletions in the azoospermic factor (AZF) on the Yq chromosome is an accepted means of identifying a common genetic cause of male infertility, responsible for 5-15% of cases associated with a low sperm count (相似文献   

Molecular screening for Yq microdeletion in men with idiopathic oligozoospermia and azoospermia

Infertility affects 15% couples attempting pregnancy and in 40–50% of these cases the male partner has qualitative or quantitative abnormalities of sperm production. Microdeletions in the azoospermia factor (AZF) region on the long arm of the Y chromosome are known to be associated with spermatogenic failure and have been used to define three regions on Yq (AZFa, AZFb and AZFc) which are critical for spermatogenesis and are recurrently deleted in infertile males. Semen analysis was carried out on one hundred and twenty five infertile males with oligozoospermia and azoospermia. Cytogenetic analysis was done for all the cases and in all cytogenetically normal cases (n = 83) microdeletion analysis was carried out on DNA extracted from peripheral blood using PCR. The sequence tagged sites (STS) primers sY84, sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc) were used for each case. Eight of the eighty three cases (9.63%) showed deletion of at least one of the STS markers. Correlation of phenotype with microdeletion was done in each case to determine any phenotype association with deletion of particular AZF locus. Based on the present study, the frequency of microdeletion in the Indian population is 9.63%. This study emphasizes the need for PCR analysis for determining genetic aetiology in cases with idiopathic severe testiculopathy.     

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。     

QF-PCR筛查男性不育患者Y染色体无精子症因子微缺失

为评估定量荧光PCR(Quantitative fluorescent polymerase chain reaction, QF-PCR)技术在快速筛查无精子症因子(Azoospermia factor, AZF)微缺失中的应用, 文章对1218例非梗阻性无精子症、少精子症的男性不育患者, 采用多重QF-PCR结合毛细管电泳技术, 检测Y染色体长臂AZF区9个序列标签位点(Sequence tagged site, STS)以及性染色体短臂的AMEL(Amelogenin)和SRY(Sex-determining region of Y chromosome)位点, 辅以常规染色体G显带方法进行核型分析。结果显示, 1218例患者中105例可见AZF区微缺失(8.62%), 其中AZFc区缺失(67.62%)最常见, 其次为AZFb,c区缺失(20.95%); AZFb区缺失(7.62%)和AZFa区缺失(3.81%)则较少见; 另有5例患者为AZFa,b,c区缺失合并AMEL-Y缺失, 提示可能缺少Y染色体, 经核型分析验证为46,XX(性反转)。105例AZF区微缺失患者的染色体核型分析显示染色体异常16例, 其中“Yqh-”12例。根据AMEL-X/AMEL-Y比值, 可见1218例患者中86例可能存在性染色体异常, 经核型分析验证, 68例为性染色体非整倍体。多重QF-PCR技术, 一个反应即能检测样本的多个位点, 并可提示性染色体是否存在异常, 有助于男性不育患者尽早明确病因, 也为后续的检查和治疗提供依据。     

Y-chromosome haplotypes in azoospermic Israeli men

Among azoospermic and severely oligozoospermic men, 7-15% present microdeletions of a region on the long arm of the Y chromosome that has been called AZF (azoospermia factor). Because these deletions present varying relative frequencies in different populations, we decided to ascertain whether their presence was correlated with specific Y-chromosome haplotypes. For that, we evaluated 51 infertile Israeli men, 9 of whom had microdeletions in AZF. Haplotypes were identified using a hierarchical system with eight biallelic DNA markers. We also checked for the presence of the deletion marker 50f2/C, which was absent in all seven patients with isolated AZFc deletion and also in the one patient with isolated AZFb deletion, suggesting that these microdeletions overlap. As expected, haplogroup J was the most common (47%), followed by equal frequencies of haplogroups Y* (xDE, J, K), P* (xR1a, R1b8), K* (xP), and E. In six patients with AZFc deficiencies of comparable size, three belonged to haplogroup J, two belonged to haplogroup P* (xR1a, R1b8), and one belonged to haplogroup R1a. Also, there were no significant differences in the haplotype frequencies between the groups with and without microdeletions. Thus we did not identify any association of a specific haplogroup with predisposition to de novo deletion of the AZF region in the Israeli population.     

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.     

Yq microdeletions--azoospermia factor candidate genes and spermatogenic arrest.

In the last few years considerable progress has been made in the study of sperm physiology and the biology of gamete interaction, furthering our understanding of the pathophysiology of male infertility. With the advent of assisted reproductive technology and intracytoplasmic sperm injection, study of the various factors leading to spermatogenic impairment has become a major focus of scientific research. Understanding the genetic factors that lead to infertility has taken on a certain urgency, as we have learned not only of the transmission to male offspring of spermatogenic impairment, but that these offspring may also be born with a secondary, larger deletion with worsening of phenotype and genital ambiguity.Ten to twenty-five percent of couples encounter difficulty procreating. Microdeletions of the long arm of the Y chromosome are associated with spermatogenic failure and have been used to define three regions on Yq (AZFa, AZFb, and AZFc) that are critical for spermatogenesis. This study was conceived in order to identify the frequency of submicroscopic interstitial deletions in azoospermia factor loci in infertile Indian males. One hundred and seventy five males with nonobstructive oligozoospermia and azoospermia were included in this study. Semen analysis was done in each case to determine the spermatogenic status-normospermic, oligozoospermic (< 20 million sperm/mL), or azoospermic (no sperm in the semen). Detailed medical, clinical, reproductive, and family histories were taken of each patient. Thirty G-banded metaphases were analyzed in each case and polymerase chain reaction microdeletion analysis was done in 133 cytogenetically normal cases. For this genomic, DNA was extracted using peripheral blood. The sequence tagged site primers tested in each case were sY84, sY86 (AZFa); sY113, sY116, sY127, sY134 (AZFb); sY254, sY255 (AZFc). Polymerase chain reaction amplifications found to be negative were repeated at least three times to confirm the deletion of a given marker. The polymerase chain reaction products were analyzed on a 1.8% agarose gel. Eight of the 133 cases showed deletion of at least one of the sequence tagged site markers. Review of the literature has shown that the overall frequency of microdeletions varies from 1% to 55%. In the present study the frequency of microdeletion was 6.01%. Deletions were detected in cases with known and unknown etiology with bilateral severe testiculopathy.     

Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion

Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined, 9 (azoospermia -8 and oligoasthenospermia -1) showed partial deletion of AZF. The size of deletion varied among patients but AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the genotype. The frequency of Y-chromosome microdeletion in our samples (∼ 5%) is much lower than the frequency (∼ 10%) reported globally and the two previous reports from India. We contend that the frequency may be affected by population structures in different geographical regions.     

Y chromosome microdeletions in Brazilian fertility clinic patients

Microdeletions in Yq are associated with defects in spermatogenesis, while those in the AZF region are considered critical for germ cell development. We examined microdeletions in the Y chromosomes of patients attended at the Laboratory of Human Reproduction of the Clinical Hospital of the Federal University of Goiás as part of a screening of patients who plan to undergo assisted reproduction. Analysis was made of the AZF region of the Y chromosome in men who had altered spermograms to detect possible microdeletions in Yq. Twenty-three patients with azoospermia and 40 with severe oligozoospermia were analyzed by PCR for the detection of six sequence-tagged sites: sY84 and sY86 for AZFa, sY127 and sY134 for AZFb, and sY254 and sY255 for AZFc. Microdeletions were detected in 28 patients, including 10 azoospermics and 18 severe oligozoospermics. The patients with azoospermia had 43.4% of their microdeletions in the AZFa region, 8.6% in the AZFb region and 17.4% in the AZFc region. In the severe oligozoospermics, 40% were in the AZFa region, 5% in the AZFb region and 5% in the AZFc region. We conclude that microdeletions can be the cause of idiopathic male infertility, supporting conclusions from previous studies.     

Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection

Cytogenetic and molecular deletion analyses of azoospermic and oligozoospermic males have suggested the existence of AZoospermia Factor(s) (AZF) residing in deletion intervals 5 and 6 of the human Y-chromosome and coinciding with three functional regions associated with spermatogenic failure. Nonpolymorphic microdeletions in AZF are associated with a broad spectrum of testicular phenotypes. Unfortunately, Sequence Tagged Sites (STSs) employed in screening protocols range broadly in number and mapsite and may be polymorphic. To thoroughly analyze the AZF region(s) and any correlations that may be drawn between genotype and phenotype, we describe the design of nine multiplex PCR reactions derived from analysis of 136 loci. Each multiplex contains 4-8 STS primer pairs, amplifying a total of 48 Y-linked STSs. Each multiplex consists of one positive control: either SMCX or MIC2. We screened four populations of males with these STSs. Population I consisted of 278 patients diagnosed as having significant male factor infertility: either azoospermia, severe oligozoospermia associated with hypogonadism and spermatogenic arrest or normal sperm counts associated with abnormal sperm morphology. Population II consisted of 200 unselected infertile patients. Population III consisted of 36 patients who had previously been shown to have aneuploidy, cytological deletions or translocations involving the Y-chromosome or normal karyotypes associated with severe phenotype abnormalities. Population IV consisted of 920 fertile (control) males. The deletion rates in populations I, II and III were 20.5%, 7% and 58.3%, respectively. A total of 92 patients with deletions were detected. The deletion rate in population IV was 0.87% involving 8 fertile individuals and 4 STSs which were avoided in multiplex panel construction. The ability of the nine multiplexes to detect pathology associated microdeletions is equal to or greater than screening protocols used in other studies. Furthermore, the data suggest a fourth AZF region between AZFb and AZFc, which we have termed AZFd. Patients with microdeletions restricted to AZFd may present with mild oligozoospermia or even normal sperm counts associated with abnormal sperm morphology. Though a definitive genotype/phenotype correlation does not exist, large deletions spanning multiple AZF regions or microdeletions restricted to AZFa usually result in patients with Sertoli Cell Only (SCO) or severe oligozoospermia, whereas microdeletions restricted to AZFb or AZFc can result in patients with phenotypes which range from SCO to moderate oligozoospermia. The panel of nine multiplexed reactions, the Y-deletion Detection System (YDDS), provides a fast, efficient and accurate method of assessing the integrity of the Y-chromosome. To date, this study provides the most extensive screening of a proven fertile male population in tandem with 514 infertile males, derived from three different patient selection protocols.     

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.     

Y染色体单倍群与西南地区男性生精障碍的相关性

男性不育中, 原发无精、少精是最为重要的因素之一, 核型异常和无精子症因子(Azoospermia factor, AZF)微缺失能解释部分原发无精、少精的原因, 然而还有许多致病因素尚不清楚。Y染色体作为男性特有的染色体, 与男性生殖系统的正常功能密切相关。文章主要对Y染色体单倍群这一分子遗传背景与男性原发无精、严重少精症之间是否存在相关性进行探讨, 为进一步探索原发无精、严重少精症的遗传学致病原因提供依据和可行的方向。采集265名生精障碍患者(原发无精症患者193名, 原发严重少精症患者72名)以及193名正常男性样本的外周血, 进行核型分析和AZF缺失分析, 以排除有此两类异常的样本。将经过筛选的样本进行Y染色体单倍群分析, 并对其单倍群分布情况进行统计分析。分析显示, 生精障碍组和对照组分别在D1*、F*、K*、N1*和O3* 上有显著性差异(P=0.032, 0.022, 0.009, 0.009, 0.017, <0.05)。Y染色体单倍群, 这一Y染色体遗传背景与男性原发生精障碍的发生有相关性。     

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.