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。     

Y染色体微缺失与男性不育关系研究进展

男性不育越来越引起人们的重视，在不育原因的研究中发现Y染色体微缺失占有一定的比例。本文就Y染色体微缺失研究进展做一综述，探讨其与男性不育的关系，更好地为临床实施辅助生育技术提供遗传咨询。     

Y染色体微缺失与男性不育关系研究进展

男性不育越来越引起人们的重视,在不育原因的研究中发现Y染色体微缺失占有一定的比例。本文就Y染色体微缺失研究进展做一综述,探讨其与男性不育的关系,更好地为临床实施辅助生育技术提供遗传咨询。     

全血直接多重PCR法快速检测Y染色体微缺失

目的 以全血为起始模板直接进行PCR多重扩增,建立一种快速、简便的Y染色体微缺失检测方法.方法 用作者自行研制的"HpH-Buffer",以不经基因组DNA提取的抗凝全血为模板直接进行多重PCR扩增.分别在5管中检测无精症因子(azoospermia factor,AZF)区域的a区、b区和c区共12个序列标签位点(sequence tagged sites,SIS).为保证方法有效性,加做Y染色体性别决定区(sex-determining region Y,SRY)和X/Y连锁锌指蛋白基因(X-linked or Y-linked zinc finger gene,ZFX/Y)作为内控.同时,为考察方法的准确性,对每例血液样本提取基因组DNA平行实验.结果 共检测了156例男性血液样本,每组实验均加做阳性对照(正常已生育男性样本)和阴性对照(正常女性样本),以保证实验有效性.结果表明,156例样本中有144例无缺失,AZFa区缺失1例,AZFb区缺失1例,AZFc区缺失7例,AZFb和AZFc区缺失1例,AZFa、AZFb和AZFc区全缺失2例.以全血为模板和以基因组DNA为模板进行扩增所得到的实验结果完全一致.结论 所建立的方法省略了DNA提取这一繁琐的步骤,减少了PCR实验过程中可能出现的污染,缩短了操作时间,节约了实验成本.可在2小时内完成所有检测过程,有效地提高了临床检测效率."HpH-Buffer"的试剂成本很低,全部检测成本与普通PER扩增基本相同.     

男性不育患者Y染色体微缺失与性激素水平相关

目的 分析Y染色体微缺失模式及与性激素水平之间关系,为男性不育患者的诊断与治疗提供依据.方法 使用多重PCR技术对798例男性不育患者进行15个序列标签位点的Y染色体微缺失检测,使用电化学发光技术检测性激素,同时检测100名男性作对照.结果 789例男性不育患者中共发现40例Y染色体微缺失,其中27例为无精子症患者,12例为严重少精子症患者.Y染色体最常见缺失区域为AZFc,最常见缺失模式为SY254+SY255.AZF区缺失不育患者组FSH水平明显高于无AZF区缺失不育患者组及男性对照组(P＜0.05).结论 AZFc区为Y染色体最常见的缺失区域,SY254+ SY255为最常见缺失模式,FSH水平在AZFc微缺失患者中水平明显升高.     

精子发生障碍患者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Y染色体上无精子症因子(azoospermicfactor,AZF)微缺失情况,建立Y染色体微缺失的分子诊断的临床筛查方法,分析原发性无精子症和少精子症患者与Y染色体微缺失的关系。方法采用多重PCR、凝胶电泳技术对56例无精子症和少精子症患者的10个STS位点或基因进行检测与筛查。结果20例精子密度正常的生育男性未检测出Y染色体微缺失;56例无精子症和少精子症患者中有9例有AZF区域的微缺失,总缺失率16.1%(9/56),AZFc/DAZ区发生微缺失频率较高。结论Y染色体微缺失是导致男性不育患者精子发生障碍的重要原因之一,AZF侯选基因在精子发生过程中可能起重要作用。     

染色体核型异常男性不育患者Y染色体微缺失分析

目的探讨染色体核型异常与Y染色体微缺失之间的关系。方法578例男性不育患者均来自2007年6月至2008年5月吉林省生殖医学研究所临床门诊。所有患者临床表现均为无精子症或严重少精子症。外周血淋巴细胞培养常规染色体标本制备,进行染色体核型分析。应用多重聚合酶链反应技术,采用无精子因子区9个序列标签位点对所有染色体异常的无精子症或严重少精子症患者进行Y染色体微缺失分析。结果578例遗传咨询患者中,检测出染色体核型异常患者62例,异常率为10.73%。其中包括无精子症或严重少精子症患者10例,占总样本1.73%。10例染色体核型异常患者检测出Y染色体微缺失2例,占20%。核型为46,XX/47,XX,＋del（Y）（q11）患者临床表现为睾丸小,无精症,Y染色体缺失位点为sY157、sY152、sY254、sY255;核型为45,X,-Y,-15,＋t（Y：15）（p？;q11）患者临床表现为特发性无精子症,缺失位点为sY143、sY254、sY255。结论涉及到Y染色体的染色体核型异常与AZF微缺失密切相关。     

200例男性不育患者的Y染色体微缺失检测

目的探讨男性不育患者与Y染色体微缺失之间的关系。方法利用15个Y染色体特异序列标签位点,以多重PCR法检测男性不育患者的Y染色体微缺失情况。结果 200例男性不育患者中共检出Y染色体微缺失7例,缺失率为3.5%。其中单纯A;ZFc缺失2例,缺失率为1%(2/200);A;ZFb缺失率为3例,缺失率为1.5%(3/200);单纯A;ZFa缺失2例,缺失率为1%(2/200),尚未发现联合缺失或大片段缺失患者。精液正常者(对照组)30例未发现Y染色体微缺失。结论 Y染色体微缺失是造成男性不育的常见病因之一。     

1011例男性不育患者Y染色体无精子症因子微缺失的筛查与临床表型分析

目的 探讨四川地区近6年不育男性Y染色体无精子症因子(azoospermia factor,AZF)微缺失的发生率、缺失类型及其与临床表型的关系.方法 应用多重PCR方法对713例非梗阻性无精症和298例重度少精症的男性进行Y染色体AZF微缺失分析.结果 AZF总体缺失率为10.48％ (106/1011),其中非梗阻性无精症患者缺失率为11.08％ (79/713),重度少精症患者缺失率为9.06％ (27/298).AZFa与AZFb完全缺失者均表现为无精症.AZFc缺失为最常见缺失类型且具有多种表型,占60.38％,其中37.50％的缺失者精液中有成熟精子.2例AZFb和1例AZFb-c部分缺失者精子密度呈轻度下降.结论 AZFc区是Y染色体AZF微缺失的缺失热点,AZFa或AZFb缺失者以及部分AZFc缺失者均表现为无精症.本研究进一步明确了AZF缺失基因型与表型的关系,证实Y染色体AZF微缺失检测对诊断男性不育具有重要的价值.     

广西地区男性不育患者Y染色体微缺失结果分析及遗传效应

目的探讨广西地区男性不育患者Y染色体微缺失结果情况和临床遗传效应。方法采用染色体技术、PCR技术等对2180例男性不育患者进行外周血染色体分析及Y染色体微缺失6个系列标签位点检测。结果 2180例样本Y染色体AZF基因检测和Y染色体异常分别为总缺失率为6%（130/2180）和3.3%（71/2180）。同时发现Y染色体AZF基因缺失在生精障碍组与正常组、不孕产史组具有统计学意义;Y染色体核型以小Y和染色体多态性常见。结论男性不育患者与Y染色体微缺失及细胞核型所表现临床遗传效应密切相关,对于生殖异常的男性行外周血染色体检查和AZF微缺失检测有助于明确其遗传学病因,更好的为患者提供病因诊断、遗传咨询和治疗方案。     

Screening for Y chromosome microdeletions in 226 Slovenian subfertile men.

BACKGROUND: The objective of this study was to estimate the frequency of Y chromosome microdeletions in the Slovenian population of infertile men and to analyse the consequences of mutation in respect to clinical severity and prognosis. METHODS: In a controlled clinical study at the university-based medical genetics service and infertility clinic, 226 infertile men undergoing ICSI were tested. The main outcome measures included polymerase chain reaction amplification of 16 genes and gene families and 42 sequence-tagged sites in the non-recombining region of the Y chromosome, semen, testicular volume and testicular histological analysis, serum FSH concentrations, fertilization and respective pregnancy rates. RESULTS: The incidence of deletions was 4.4%: 8.6% in men with azoospermia and 1.5% in men with oligoasthenoteratozoospermia. Isolated gene deletions were not identified. No statistically significant differences in clinical outcome measures were found in patients with mutations versus patients without mutations. High fertilization (49%) and pregnancy (43%) rates with sperm of patients with Y chromosome deletions were obtained. CONCLUSIONS: Testing for gene-specific microdeletions does not contribute significantly to the sensitivity of microdeletion test. Fertilization and pregnancy rates obtained using sperm of patients with Y chromosome deletions were comparable with those achieved in conventional IVF.     

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.     

Y染色体变异与男性不育

男性不育是一种常见的复杂疾病,Y染色体连锁生精障碍是该病的一个重要病因.Y染色体男性特异性区域存在大量的重复序列,这些序列间频发的染色体内非等位性同源重组,使Y染色体具备了高变异率的特点,这些结构变化较易引起生精相关基因的剂量改变,进而导致男性不育.作者对近年来DNA水平上男性不育相关的Y染色体变异研究进行了综述.     

Y chromosome microdeletion screening in infertile men in France: a survey of French practice based on 88 IVF centres

Y chromosome microdeletion screening is advised in cases of severely impaired spermatogenesis. Improvements in molecular biological techniques have made diagnosis more accessible in routine analysis. However, Y chromosome microdeletions are not diagnosed in all IVF centres. The aim of the present study was to determine the regulatory (indications, financing) and performance (methods, invoicing) conditions required for this analysis, in France. Microdeletion detection was found to be spreading fast and consistantly. It therefore seems necessary for a consensus to be reached on indications, with a view to a standardized technique, with a common effort of experts in the field. Financial management by the French Health Insurance bodies (Sécurité Sociale) would be an essential step towards routine adoption. Lastly, the answers to our questionnaire revealed a strong demand for information concerning this analysis.     

The Y chromosome gr/gr subdeletion is associated with male infertility

Men with Y chromosome (Yq) AZFc deletions lack all copies of the DAZ gene and have severe spermatogenic failure. A recently described gr/gr subdeletion of AZFc removes two of four copies of DAZ. To better understand the relative frequencies of AZFc and gr/gr deletions and their associated phenotypes, we analysed two large groups of infertile men. A total of 788 men from the Monash Male Infertility (MMI) database with a range of fertility disorders showed similar overall prevalences of AZFc (2.5%) and gr/gr deletions (3.4%). There was no association of gr/gr deletions with sperm density. In 234 control men of known or presumed fertility, only one gr/gr deletion was found. In a further 599 consecutive men presenting for assisted reproductive technologies, we detected 13 (2.2%) AZFc deletions and 28 (4.7%) gr/gr deletions. All AZFc deletions were seen with sperm densities <5 million/ml but again the gr/gr deletion occurred with similar frequency across all sperm density categories. These data show that gr/gr deletions are significantly associated with infertility in the Australian population (P = 0.0015) but not exclusively with reduced sperm density suggesting a complex interaction with other factors important for male fertility. Vertical transmission of gr/gr deletions from father to son by ICSI was demonstrated in four cases. Analysis of 130 ICSI-conceived sons revealed no de novo gr/gr deletions indicating that ICSI is not a risk factor. The data suggest that testing for gr/gr deletions should be considered in the routine genetic assessment of men with idiopathic infertility.     

高促卵泡成熟激素无精子症患者Y染色体微缺失检测

目的　探讨高促卵泡成熟激素 (follicle- stimulating hormone,FSH)无精子症与 Y染色体基因微缺失的关系。方法　采用 PCR技术对 16例高 FSH无精子症患者 Y染色体长臂上 11个序列标记位点进行微缺失的检测。结果　 16例高 FSH无精子症不育男性中 6例存在 Y染色体序列标记位点的微缺失 ,缺失率为 37.5 % (6 / 16 ) ,缺失形式有 5种 ,分别为 AZFc(SY15 2 )、AZFc(SY15 2 SY2 5 4 ) AZFd(SY15 3)、AZFc(SY15 2 SY2 5 4 SY2 5 5 ) AZFd(SY15 3)、AZFc(SY15 2 SY15 8 SY2 5 5 ) AZFd(SY15 3)、AZFb(SY130 ) AZFc(SY15 8 SY2 5 4 SY2 5 5 ) AZFd(SY15 3)。结论　 Y染色体微缺失是高FSH无精子症患者的重要原因之一 ,对高 FSH无精子症患者实施辅助生育技术时非常有必要先进行 Y染色体基因微缺失的检测 ,特别是检测 AZFc、AZFd等区域。