Klinefelter综合征患者Y染色体AZF微缺失分析

目的观察Klinefelter综合征患者Y染色体AZF微缺失发生情况。方法12例Klinefelter综合征患者ICSI/IVF等辅助受孕前进行睾丸细针穿刺吸液细胞学检查及Y染色体AZF微缺失分析。确定8个实验用序列标签位点（STS）,分别是：sY84、sY86、sY127、sY134、sY152、sY153、sY254、sY255,并以X/Y连锁锌指蛋白基因（ZFX/Y）为内对照进行多重PCR筛查AZF微缺失。结果睾丸细针穿刺吸液细胞学检查显示,3例（25.0%,3/12）可见到极少量形态较完整的精子及各级生精细胞、精子细胞,7例（58.3%,7/12）仅见少量生精细胞及精子细胞,2例（16.7%,2/12）仅见支持细胞,未见生精细胞及精子。12例Klinefelter综合征患者共检测出AZF微缺失2例分别为AZFa＋AZFc区缺失和AZFb＋AZFc区缺失;对照组32例样本未检出AZF基因微缺失。KS患者AZF微缺失检出率与对照组比较有显著差异（χ^2=5.587,P=0.018）。结论Klinefelter综合征患者存在Y染色体长臂AZF微缺失,缺失率为16.7%。     

无精和严重少精子症患者Y染色体的微缺失

目的 检测我国无精和严重少精子症患者Y染色体微缺失的发生情况和位点,及其与睾丸病理学类型的关系.方法 取584例无精子症和80例严重少精子症患者精液中细胞或外周血白细胞,裂解提取DNA,用4组多重聚合酶链反应检测分布于AZFa、AZFb、AZFc区,包括欧洲男科学会和欧洲分子遗传学质量控制体系推荐的6个位点在内的共15个序列标签位点(sequence tagged site,SIS)的缺失.对部分有Y染色体微缺失患者进行睾丸细针抽吸活检,检查睾丸病理学类型.结果 584例无精子症患者中,共有66例(11.3%)发生Y染色体微缺失,各区发生率构成比由高到低依次为:AZFc区48例(72.7%),AZFb+c区9例(13.6%),AZFa+b+c区4例(6.1%),AZFb区3例(4.5%),A2Fa区2例(3.0%).80例严重少精子症患者共有10例发生Y染色体微缺失(12.5%),均为AZFc区缺失.AZFc区缺失患者(19例)睾丸病理学类型多样化;AZFb+c区或AZFa+b+c区缺失患者(7例)睾丸病理学类型为唯支持细胞综合征或生精阻滞于精原细胞.结论 Y染色体微缺失在我国的发生情况与其他国家大多数报道基本一致,跨区大缺失对精子发生造成严重影响.     

No AZF deletion in 160 patients with testicular germ cell neoplasia

Testicular germ cell cancer is aetiologically linked to genital malformations and male infertility and is most probably caused by a disruption of embryonic programming and gonadal development during fetal life. In some cases, germ cell neoplasia is associated with a relative reduction of Y chromosomal material (e.g. 45,X/46,XY) or other abnormalities of the Y chromosome. The euchromatic long arm of the human Y chromosome (Yq11) contains three azoospermia factors (AZFa, AZFb, AZFc) functionally important in human spermatogenesis. Microdeletions encompassing one of these three AZF loci result in the deletion of multiple genes normally expressed in testis tissue and are associated with spermatogenic failure. The aim of our study was to investigate whether AZF microdeletions, in addition to causing infertility, predispose also to germ cell neoplasia, since subjects with poor spermatogenesis have an increased risk of testicular cancer. We screened for putative deletions of AZF loci on the Y chromosome in DNA isolated from white blood cells of 160 Danish patients with testicular germ cell neoplasia. Interestingly, although AZF microdeletions are found frequently in patients with idiopathic infertility, in all cases studied of testicular germ cell cancer the Yq region was found to be intact. We conclude that the molecular aetiology of testicular germ cell neoplasia of the young adult type most likely does not involve the same pathways as male infertility caused by AZF deletions. Malignant transformation of germ cells is thus caused by the dysfunction of some other genes that still need to be identified.     

Microdeletions in the Y chromosome in cases of male infertility in a population of West Bengal

IntroductionInfertility is a burning problem in gynecological, andrological, endocrine and genetic practice. Of the myriad factors responsible for male infertility, which may be manifested as oligozoospermia or azoospermia, the exact causes of the latter are still unknown or debatable. Among the known parameters, the occurrence of microdeletions in the long arm of the Y chromosome are of great importance, as they have been consistently associated with defects in spermatogenesis. The microdeletions of the Y chromosome have been mapped to three regions in interval 6 named azoospermia factor regions (AZF), AZFa, AZFb and AZFc.MethodsIn the present study 80 males suffering from oligozoospermia or azoospermia were taken from both rural and urban infertility clinics and subjected to Polymerase Chain Reaction (PCR) of DNA from blood samples using a total of 11 STS primers. These primers correspond to different segments of the AZF regions (AZFa, AZFb and AZFc) and are known as Sequence Tagged Sites (STS). This was followed by agar gel electrophoresis to look for deletions in the AZF regions corresponding to the STF primers.ResultThese tests were able to detect microdeletions in the long arm of the Y chromosome in 4 patients.DiscussionIn majority of patients PCR detects no abnormality but in cases having microdeletions, appropriate advice could be given to the patients. These patients were told to avoid the use of their sperm in assisted reproduction procedures and accept the use of donor sperm or adoption procedures as a solution to their problems of infertility.     

Detection of sperm in men with Y chromosome microdeletions of the AZFa,AZFb and AZFc regions

BACKGROUND: Y chromosome microdeletions are associated with severe male factor infertility. In this study, the success rate of testicular sperm retrieval was determined for men with deletions of AZF regions a, b or c. METHODS: AZF deletions were detected by PCR of 30 sequence-tagged sites within Yq emphasizing the AZFa, b and c regions. Semen analysis and diagnostic testis biopsy or testicular sperm extraction (TESE) findings were correlated with the specific AZF region deleted. RESULTS: A total of 78 men with AZF deletions included three with AZFa deletion, 11 with AZFb, 42 with AZFc, 16 with AZFb+c and six with Yq (AZFa+b+c). All men with AZFa, AZFb, AZFb+c and Yq deletions were azoospermic and no sperm were found with TESE or biopsy. Of men with isolated AZFc deletion, sperm were found in 75% (9/12) by TESE and 45% (9/20) on biopsy (56% overall); 62% (26/42) were azoospermic and 38% (16/42) severely oligozoospermic. A total of 7 patients with deletion patterns that included the complete AZFa region and 23 that included the complete AZFb region who underwent TESE or biopsy did not have sperm detected by these surgical measures. CONCLUSIONS: Microdeletion of the entire AZFa or AZFb regions of the Y chromosome portends an exceptionally poor prognosis for sperm retrieval, whereas the majority of men with AZFc deletion have sperm within the semen or testes available for use in IVF/ICSI.     

AZF deletions and Y chromosomal haplogroups: history and update based on sequence

AZF deletions are genomic deletions in the euchromatic part of the long arm of the human Y chromosome (Yq11) associated with azoospermia or severe oligozoospermia. Consequently, it can be assumed that these deletions remove Y chromosomal genes required for spermatogenesis. However, these 'classical' or 'complete' AZF deletions, AZFa, AZFb and AZFc, represent only a subset of rearrangements in Yq11. With the benefit of the Y chromosome sequence, more rearrangements (deletions, duplications, inversions) inside and outside the classical AZF deletion intervals have been elucidated and intra-chromosomal non-allelic homologous recombinations (NAHRs) of repetitive sequence blocks have been identified as their major cause. These include duplications in AZFa, AZFb and AZFc and the partial AZFb and AZFc deletions of which some were summarized under the pseudonym 'gr/gr' deletions. At least some of these rearrangements are associated with distinct Y chromosomal haplogroups and are present with similar frequencies in fertile and infertile men. This suggests a functional redundancy of the AZFb/AZFc multi-copy genes. Alternatively, the functional contribution(s) of these genes to human spermatogenesis might be different in men of different Y haplogroups. That raises the question whether, the frequency of Y haplogroups with different AZF gene contents in distinct human populations leads to a male fertility status that varies between populations or whether, the presence of the multiple Y haplogroups implies a balancing selection via genomic deletion/amplification mechanisms.     

特发性无精子症及少弱精子症患者Y染色体AZF微缺失筛查分析

目的探讨特发性无精子症及少弱精子症不育男性与Y染色体AZF微缺失的关系.方法用双重PCR技术对63例患者(无精于症41例,少弱精子症14例,严重少精子症8例)进行Y染色体AZFa、AZFb、AZFc、SRY的微缺失筛查.同时对26例无精于症患者行睾丸活检、组织学评估.结果63例中AZF微缺失7例,缺失率为11.1%.其中无精子症5例,严重少精子症2例.AZFc缺失4例,AZFb缺失2例,AZFb AZFc缺失1例,未发现AZFa区缺失.63例及对照组30例SRY基因扩增均阳性.26例无精子症患者行睾丸活检、组织学检查,无1例精子发生正常.结论Y染色体微缺失,特别是AZFc区DAZ基因的微缺失,是引起无精子和严重少弱精子等生精障碍而致男性不育较为重要的遗传学因素.     

Mice with Y chromosome deletion and reduced Rbm genes on a heterozygous Dazl1 null background mimic a human azoospermic factor phenotype

A subset of azoospermia or oligozoospermia patients have microdeletions in defined regions of their Y chromosome, namely the AZFa, b, and c regions. Candidate genes in humans that may cause the azoospermia factor (AZF) phenotype have been assigned to these regions and can include the DAZ and RBM genes. Part of the variability in the AZFc phenotype might be due to interaction between the effects of deleting the DAZ and RBM genes. We mimicked human deletions of RBM and DAZ in the mouse by crossing male mice with a deleted Y chromosome with a reduced number of Rbm genes (Y(d1)) to heterozygote Dazl1 null female mice to study the interaction of the Dazl1 and Rbm or other genes located in the Y(d1) deletion interval. Dazl-/+ Y(d1) animals showed a significant reduction in the sperm count (P < 0.001), an increase of abnormal sperm heads and prominent mid-piece defects of the tails compared to either mutation alone (P < 0.001). Hence, Dazl1 and the genes removed on the Y(d1) chromosome are active in different pathways contributing to different stages of spermatogenesis. Reduction of Dazl1 and Rbm genes as well as/or deletion of the Y chromosome in mice gives rise to a phenotype similar to the heterogeneous AZFc phenotype observed in humans.     

不育男性的AZF检测与Y染色体缺失的对照分析

目的探讨精子发生障碍的男性不育患者AZF缺失与Y染色体缺失的临床意义。方法对616例非阻塞性无精子症或少精子症患者进行AZF的检测,同时观察G显带Y染色体的形态。结果从616例患者中检测出48例患者分别为AZFa、AZFb、AZFc或AZFb+AZFc的微缺失,但显微镜下观察不到Y染色体形态改变。另外4例患者经AZF检测,2例为AZFc+sY160缺失,1例为AZFb+AZFc+sY160缺失,1例为AZFa+AZFb+AZFc+sY160缺失,显微镜下发现Yq部分或完全缺失。25例已育男性的G-显带的Y染色体和AZF也进行对照检测,均未发现AZF的缺失,但其中1例核型分析显示Y染色体长臂部分缺失,但PCR检测仅缺失sY160,即Yq12的缺失。结论Yq11.23上7Mb的缺失在细胞水平不能分辨。q11.23+q12的缺失或仅有Yq12的缺失的Y染色体显微镜下不能区分,但后者不是精子发生障碍的病因。对男性不育精子发生障碍患者,要结合细胞遗传学和AZF分子检测综合判断。     

Manifestation of Y-chromosomal deletions in the human testis: a morphometrical and immunohistochemical evaluation

BACKGROUND: Deletions of the AZF (azoospermia factor) subregions on the Y chromosome are accompanied by a diverse spectrum of spermatogenic disturbances ranging from hypospermatogenesis to total depletion of germ cells causing infertility. The AZF region encodes gene products which are candidates for the genetic control of spermatogenesis. Although it is known which genes are involved, a general principle of cause and effect cannot yet be deciphered and the deletion type has non-uniform histological phenotypes. METHODS AND RESULTS: We analysed morphological parameters of testicular biopsies from 17 patients diagnosed for Y chromosome microdeletions. As control groups we analysed testes from patients with idiopathic Sertoli cell-only (SCO) syndrome (n = 11), mixed atrophy (n = 10) and complete spermatogenesis (n = 11). A detailed genetic analysis on the extension of the observed microdeletions revealed similar breakpoints in the distal and proximal region of the AZFc region, indicating a common mechanism of homologous recombination for such deletions, as has been suggested before. Morphometric parameters such as the diameter of the tubules, lumen, thickness of the lamina propria and height of the tubule epithelia were investigated. The diameter of the tubules from patients with microdeletions was found to be significantly smaller compared with patients with mixed atrophy. Considering also the size of the tubules, lumen and epithelia, a Y-chromosomal microdeletion represents an intermediate state between an idiopathic SCO and normal spermatogenesis. The immunohistochemical analysis of six different Sertoli cell markers, cytokeratin 18, vimentin, inhibin alpha subunit, 14-3-3 theta, FSH receptor and androgen receptor, revealed no impact of AZF deletion on the specific expression pattern of these genes. CONCLUSIONS: Our results suggest that, notwithstanding the deletion of a common region in the AZFc region, microdeletions of the Y chromosome lead to an intermediate status between idiopathic SCO and complete spermatogenesis, resulting in a heterogeneous histological profile regardless of the seminiferous activity. The Sertoli cell function seems not to be altered.     

Analysis of Yq microdeletions in infertile males by PCR and DNA hybridization techniques

Defects in spermatogenesis have been found associated with deletions of different portions of Y chromosome long arm (Yq), suggesting the presence of the azoospermia factor in the control of spermatogenesis. We studied 67 men with idiopathic azoospermia and severe oligozoospermia, cytogenetically normal, for the presence of microdeletions on Yq chromosome. By using polymerase chain reaction (PCR) and Southern blotting techniques we analysed the AZFa, AZFb and AZFc loci on Yq, where deletions have been associated with defects in spermatogenesis. Deletions of a portion of the Y chromosome were detected in five patients. Four of these patients shared deletions in distal Yq11 interval 6, including the DAZ gene, while one patient lacked loci in the proximal Yq11. Testicular histology of two patients bearing distal Yq11 deletions showed two different spermatogenic defects including Sertoli cell-only (SCO) syndrome and maturation arrest, while the patient with microdeletions in the proximal Yq11 showed a SCO phenotype.      

Y chromosome microdeletions in Tunisian infertile males

AIM: To determine frequency of Y microdeletions in azoospermic and oligospermic Tunisian infertile males. METHODS: A Sample of 146 Tunisian infertile males with a low sperm count (<5 x 10(6) sperms per mililiter) and normal karyotype was screened for Y chromosome microdeletions. 76 men were azoospermic and 70 men were oligospermic. Genomic DNA was isolated from blood and multiplex PCR was carried out with a set of 20 AZFa, AZFb and AZFc STS markers to detect the microdeletions as recommended by the European Academy of Andrology. RESULTS: In 10/146 (6.85%) subjects AZF deletions were observed. Of these ten males with microdeletions, 9/10 subjects were azoospermic (90%), 1/10 was oligospermic (10%). Frequency of microdeletions in azoospermic men was 9/76 (11.84%). None of the patients showed isolated microdeletion in the AZFa region, but one azoospermic man had deletion in the AZFb region. Eight azoospermic patients and one oligospremic man have AZFc microdeletions. AZFc and AZFb were deleted in three azoospermic patients. AZFc, AZFb and AZFa were deleted in three azoospermic patients We estimate the sensitivity of the test comprising six STS in our sample to be 90%. CONCLUSION: The incidence of Yq microdeletions in the study population of infertile Tunisian men falls within the range published in other countries. We suggest to analyze 9STS in the first step to detect efficiently Y microdeletions in our population.     

Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y chromosome.

We have used a series of 30 DNA probes previously mapped to the long arm of the human Y chromosome, to screen a panel of 21 patients with structural abnormalities in Yq, by genomic blot hybridisation. The results have allowed us to construct a detailed map of interval 6 of the Y chromosome, in which 28 of the probes could be assigned to 14 sub-intervals within interval 6. Some probes detect two or more loci within this region, each of which has been localised. The same set of probes has been used to screen a panel of 19 chromosomally normal azoospermic men, two of whom have been found to carry microdeletions within this region. With the completion of this map we have been able accurately to localise these microdeletions within interval 6 and show that they do not overlap. We believe these microdeletions may disrupt the azoospermia factor (AZF) involved in spermatogenesis, and which is known to lie in this region. These results are an important step towards the localisation of the AZF locus.     

150例无精子和少精子症患者Y染色体AZF区微缺失检测及染色体核型分析

目的分析无精子和少精子症患者Y染色体AZF基因微缺失与染色体核型的关联。方法对无精子、少精子症男性患者Y染色体AZF基因区15个STS位点进行检测和染色体核型分析。结果 150例患者经15个STS位点检测发现AZF区微缺失12例,总缺失率为8.0%。其中AZFa缺失2例,缺失频率为1.3%;AZFb缺失1例,缺失频率为0.6%;AZFc缺失11例,缺失频率为7.3%;AZFd缺失10例,缺失频率为6.7%。AZF区缺失频率为AZFc〉AZFd〉AZFa〉AZFb。12例AZF区微缺失的患者共存在4种缺失类型,其中10例患者为AZF区的联合缺失。所有患者经核型分析共检测出14例异常核型,异常率为9.3%。14例异常核型患者中有1例存在Y染色体微缺失;136例正常核型患者存在11例Y染色体微缺失。结论 Y染色体AZF区有缺失,不一定染色体核型异常,染色体核型异常也不排除有AZF的缺失;Y染色体微缺失与染色体核型异常不呈一一对应关系。     

Detection of Y chromosome microdeletions in AZF region by liquid chip technology]

OBJECTIVE: To establish a liquid chip technology to detect Y chromosome microdeletions in Chinese infertile males with azoospermia or oligozoospermia. METHODS: Multiplex PCR and liquid chip technology were used to detect the Y chromosome microdeletions in AZF region in 178 infertile patients with azoospermia and 134 infertile patients with oligozoospermia as well as 40 fertile control men. RESULTS: Forty out of 312 patients (12.8%) were found to have deletions in AZF region. The microdeletion frequency was 14%(25/178) in the azoospermic group, 9.6%(11/114) in the oligospermic and 20%(4/20) in the severe oligospermic group. CONCLUSION: The authors developed a high-throughput, fast and simple assay to screen the AZF region microdeletions of Y chromosome.     

COMMENTS

Human spermatogenesis is regulated by a network of genes located on autosomes and on sex chromosomes, but especially on the Y chromosome. Most results concerning the germ cell function of the Y genes were obtained by genomic breakpoint mapping studies of the Y chromosome of infertile patients. Although this approach has the benefit of focussing on those Y regions that contain most likely the Y genes of functional importance, its major drawback is the fact that fertile control samples were often missing. In fertile men, molecular and cytogenetic analyses of the Y chromosome has revealed highly polymorphic chromatin domains especially in the distal euchromatic part (Yq11.23) and in the heterochromatic part (Yq12) of the long arm. In sterile patients cytogenetic analyses mapped microscopically visible Y deletions and rearrangements in the same polymorphic Y regions. The presence of a Y chromosomal spermatogenesis locus was postulated to be located in Yq11.23 and designated as AZoospermia Factor (ZF). More recently, molecular deletion mapping in Yq11 has revealed a series of microdeletions that could be mapped to one of three different AZF loci: AZFa in proximal Yq11 (Yq11.21), AZFb and AZFc in two non‐overlapping Y‐regions in distal Yq11 (Yq11.23). This view was supported by the observation that AZFa and AZFb microdeletions were associated with a specific pathology in the patients' testis tissue. Only AZFc deletions were associated with a variable testicular pathology and in rare cases AZFc deletions were even found inherited from father to son. However, AZFc deletions were found with a frequency of 10–20% only in infertile men and most of them were proved to be “de novo”, i.e. the AZFc deletion was restricted to the patient's Y chromosome. Based mainly on positional cloning experiments of testis cDNA clones and on the Y chromosomal sequence now published in GenBank, a first blueprint for the putative gene content of the AZFc locus can now be given and the gene location compared to the polymorphic DNA domains. This artwork of repetitive sequence blocks called AZFc amplicons raised the question whether the AZFc chromatin is still part of the heterochromatic domain of the Y long arm well known for its polymorphic extensions or is decondensed and part of the Yq11.23 euchromatin? We discuss also the polymorphic DAZ gene family and disclose putative origins of its molecular heterogeneity in fertile and infertile men recently identified by the analyses of Single Nucleotide Variants (SNVs) in this AZFc gene locus.     

男性不育患者Y染色体微缺失的研究

目的研究无精子症和少精子症患者与Y染色体位点缺失的相关性，建立Y染色体微缺失的分子诊断方法。方法采用多重PCR技术对53例染色体核型正常的无精子症和少精子症患者以及5例正常男性的无精子因子（azoospermia factor，AZF）区域的6个STS位点进行检测。结果5例精液正常男性未检出Y染色体微缺失；53例患者中6例有AZF区域的微缺失，总缺失率为11．3％。结论Y染色体微缺失是严重生精障碍的重要原因之一，无精子因子（AZF）候选基因在精子发生过程中可能起重要作用。     

Polymorphic DAZ gene family in polymorphic structure of AZFc locus: Artwork or functional for human spermatogenesis?

Human spermatogenesis is regulated by a network of genes located on autosomes and on sex chromosomes, but especially on the Y chromosome. Most results concerning the germ cell function of the Y genes were obtained by genomic breakpoint mapping studies of the Y chromosome of infertile patients. Although this approach has the benefit of focussing on those Y regions that contain most likely the Y genes of functional importance, its major drawback is the fact that fertile control samples were often missing. In fertile men, molecular and cytogenetic analyses of the Y chromosome has revealed highly polymorphic chromatin domains especially in the distal euchromatic part (Yq11.23) and in the heterochromatic part (Yq12) of the long arm. In sterile patients cytogenetic analyses mapped microscopically visible Y deletions and rearrangements in the same polymorphic Y regions. The presence of a Y chromosomal spermatogenesis locus was postulated to be located in Yq11.23 and designated as AZoospermia Factor (ZF). More recently, molecular deletion mapping in Yq11 has revealed a series of microdeletions that could be mapped to one of three different AZF loci: AZFa in proximal Yq11 (Yq11.21), AZFb and AZFc in two non-overlapping Y-regions in distal Yq11 (Yq11.23). This view was supported by the observation that AZFa and AZFb microdeletions were associated with a specific pathology in the patients' testis tissue. Only AZFc deletions were associated with a variable testicular pathology and in rare cases AZFc deletions were even found inherited from father to son. However, AZFc deletions were found with a frequency of 10-20% only in infertile men and most of them were proved to be "de novo", i.e. the AZFc deletion was restricted to the patient's Y chromosome. Based mainly on positional cloning experiments of testis cDNA clones and on the Y chromosomal sequence now published in GenBank, a first blueprint for the putative gene content of the AZFc locus can now be given and the gene location compared to the polymorphic DNA domains. This artwork of repetitive sequence blocks called AZFc amplicons raised the question whether the AZFc chromatin is still part of the heterochromatic domain of the Y long arm well known for its polymorphic extensions or is decondensed and part of the Yq11.23 euchromatin? We discuss also the polymorphic DAZ gene family and disclose putative origins of its molecular heterogeneity in fertile and infertile men recently identified by the analyses of Single Nucleotide Variants (SNVs) in this AZFc gene locus.     

无精子和严重少精子患者Y染色体AZF微缺失的PCR筛查

目的：探讨Y染色体上AZF微缺失与精子生成的遗传效应关系,建立对无精子症和严重少精子患者Y染色体微缺失的筛查方法。方法;本文应用聚合酶链反应（PCR）技术对无精子症和严重少精子患者进行Y染色体上AZFa,AZFb,AZFc等5个基因片段的微缺失检测。结果：在64例无精子患者中,AZFb,AZFc,RBM人率分别为4．69％、17．19％、4．69％、未发现AZFa缺失。在53例严重少精子患者中,除1例同时伴有RBM缺失外,均为AZFc缺失,未发现AZFa和AZFb缺失,缺失率为18．87％。30例正常对照组未发现5个区域缺失。结论：精子发生与Y染色体上的多个基因有关,AZFb,AZFc的微缺失是导致无精子和严重少精子的重要原因,AZFc区微缺失可作病因筛查主要候选基因。     

Prognostic value of Y deletion analysis. The role of current methods

Y chromosome microdeletions represent the most frequent genetic alteration in azoospermic and severely oligozoospermic men, and screening for microdeletions in AZFa, b and c are routinely performed in the major andrology and infertility centres. Since patients with Y microdeletions often require intracytoplasmic sperm injection (ICSI), the question of whether the type of the microdeletion present could have prognostic value for the presence of spermatozoa in the ejaculate or in the testes [by testicular sperm extraction (TESE)] is an interesting one. The review of the literature on this topic showed that there is still no clear genotype--phenotype relationship, i.e. similar testicular alterations may be caused by different types of microdeletions, and apparently identical microdeletions may be associated with diverse tubular damage. Even in azoospermic men, the localization of the microdeletion cannot be used as a valid prognostic parameter before TESE--ICSI to identify patients with spermatozoa in their testes. The only finding with absolute negative prognostic value is the presence of complete AZFa--c deletions, which are invariably associated with an absence of spermatozoa. Microdeletions in AZFa or AZFb seem to have promising prognostic value, but more data and gene-specific deletions have to be provided to draw clear conclusions. The absence of a clear genotype--phenotype relationship, and therefore of a prognostic value of Y deletion analysis, is probably due to the current methods used for the screening of the microdeletions. In fact, to date most centres do not use gene-specific markers but instead use anonymous primers that contribute little information to the pathogenic role of the microdeletions.