男性不育中Y染色体微缺失的研究进展

近年来对男性不育的遗传学因素的广泛研究显示Y染色体微缺失是导致不同程度生精障碍从而引起男性不育的第二大遗传学病因。无精子症因子区(AZF区)由近至远包含3个不同的亚区:AZFa、AZFb和AZFc,不同缺失类型的表型不同。目前常采用PCR法进行Y染色体微缺失的检测,其缺点是准确度低、特异性差、耗时。而基因芯片技术虽能克服上述缺点,但目前成本过高。通过检测能预测患者男性后代的遗传风险,有助于患者选择辅助治疗的方式。虽然Y染色体微缺失的严重不育患者能通过辅助生殖技术成功获得后代,但有可能将遗传缺陷传给男性后代,使之获得相同的Yq微缺失和不育。     

特发性无精症和严重少精症患者Y染色体微缺失的分子检测

目的 :研究特发性无精症和严重少精症患者与 Y染色体微缺失的关系 ,建立无精症和严重少精症患者 Y染色体微缺失的分子检测方法。方法 :应用 PCR技术对 1 0 0例无精症和严重少精症患者 (其中无精症 72例 ,严重少精症 2 8例 )进行 Y染色体 AZFa、AZFb、AZFc/DAZ、SRY的微缺失检测。结果 :1 2例患者 (1 2 % )有 AZFc的微缺失 (其中无精症 8例 ,占 1 1 .1 % ;严重少精症 4例 ,占 1 4.3% ) ,且其中 1例无精症患者为 AZFb、AZFc双重缺失 ;所有病例未发现有 AZFa的缺失 ;SRY基因 PCR扩增均为阳性。6 0例已有生育的正常男性均无 AZFa、AZFb、AZFc、SRY微缺失。结论 :Y染色体微缺失 ,特别是 AZFc/DAZ的缺失是引起无精和严重少精、造成男性不育的重要原因之一 ,在进行遗传咨询和行卵细胞质内注入精子术 (ICSI)时 ,有必要对不明原因的不育男性患者进行 Y染色体微缺失的分子检测     

Y染色体微缺失与辅助生殖技术关系的研究进展

Y染色体是男性特有的染色体,其长臂上的无精子因子(AZF)区域具与男性不育密切相关的基因,目前将该区域分为AZFa、AZFb、AZFc和AZFd4个区域。AZF缺失是导致男性不育的重要因素之一,可以通过辅助生殖技术(ART)遗传给下一代引起不育。研究Y染色体微缺失分类与表型关系,可以为临床治疗各种男性不育症提供分子或细胞水平的依据。Y染色体微缺失发生频率存在种族差异性;目前Y染色体微缺失的检测方法仍然以多重PCR为主;对于ICSI助孕的男性后代是否会出现新发Y染色体微缺失仍然存在争论。     

精子发生障碍患者Y染色体微缺失分子诊断

目的:通过建立的Y染色体微缺失筛查方法了解生精障碍与Y染色体微缺失的关系。方法:同时采用多重PCR-凝胶电泳技术和多重PCR-液态芯片技术对原发性无精症、少精症患者和精液常规正常男性对照进行Y染色体微缺失筛查。结果:42例无精症、少精症患者中,6例有AZF区域STS位点或基因的缺失,总缺失率为14.3%,AZFc/DAZ区发生微缺失的频率较高,AZFa区发生微缺失的频率较低。结论:本研究建立的Y染色体微缺失多重PCR-MASA检测系统具有相对高通量、简便、快速、特异性强、敏感性高等特点;染色体微缺失是导致男性精子发生障碍的重要原因之一,AZF的候选基因在精子发生过程中可能起重要作用。     

Y染色体基因微缺失与男性不育的关系

目的 :探讨男性不育患者尤其是特发性无精子症、严重少精子症及双侧输精管缺如与 Y染色体基因 (无精子因子 ,AZF)微缺失的关系。方法 :对 97例男性不育患者及 2 0例正常男性采用多重聚合酶链反应法进行基因微缺失检测。结果 :36例特发性无精症患者中存在 3例缺失 ,占 8.33% ;1 4例双侧输精管缺如患者存在 2例缺失 ,占 1 4.2 9% ;2 7例严重少精症患者中存在 2例缺失 ,占 7.41 %。2 0例精子数正常的男性不育患者及 2 0例正常男性对照无 AZF缺失。缺失以 AZFa,AZFc区为主 ,AZFb区无缺失。结论 :Y染色体 AZF微缺失可能是导致男性特发性无精症、少精症的原因之一 ,双侧输精管缺如患者也存在 Y染色体的基因微缺失     

无精子因子AZFc微缺失的相关研究进展

Y染色体无精子因子(azoospermia factor,AZF)缺失是男性不育的重要原因,该缺失可导致男性生精障碍甚至是无精子症。AZFc缺失在AZF所有缺失类型中最为常见的,加上AZFc区域在Y染色体上的基因结构复杂,被发现有多种缺失类型,因此AZFc微缺失男性的临床表现也多样,从精子密度正常、少精到无精都可能发生。随着辅助生殖技术的发展,因AZFc缺失而严重少弱精的患者可通过辅助生育方式将这种染色体的缺陷遗传给男性子代并可能导致子代缺失的扩大;并且,因严重少弱精而通过ICSI治疗的男性,其子代AZFc微缺失的发生风险明显增加。     

Y染色体微缺失对卵胞质内单精子注射胚胎情况和临床结局的影响

目的:探讨Y染色体微缺失对卵胞质内单精子注射(ICSI)胚胎形成情况和临床结局的影响。方法:收集22例Y染色体微缺失患者进行的27个ICSI治疗周期(研究组)的胚胎和临床结局资料,另收集同期88例严重少精子症或无精子症非Y染色体微缺失患者的101个ICSI治疗周期(对照组)的相应资料进行回顾性分析;同时比较不同Y染色体微缺失类型患者进行ICSI的胚胎资料和临床结局。结果:研究组和对照组的受精率分别为84.91%与86.30%,卵裂率分别为95.45%与96.79%,优质胚胎率分别为49.35%与45.03%,新鲜周期移植优质胚胎率分别为80.36%与84.80%,临床妊娠率分别为65.22%与60.40%,胚胎着床率分别为41.07%与33.60%,早期流产率分别为0.00%与4.92%,活产率分别为56.52%与55.45%,男婴比例分别为56.25%与47.83%。各观察指标组间均无统计学差异(P>0.05)。AZFb区部分缺失组2个新鲜胚胎移植周期中有1例获得生化妊娠,但后转阴性;d区部分缺失组及d区和c区部分缺失组各1次新鲜胚胎移植周期且均未获得妊娠;d区部分缺失加c区全部缺失组19个新鲜胚胎移植周期15例获得妊娠且无一例发生流产。结论:Y染色体微缺失对ICSI治疗周期形成的胚胎情况和妊娠结局无显著性影响,但AZFd区部分缺失加c区全部缺失患者配偶临床妊娠机会高于其他类型Y染色体微缺失患者,AZFb区部分缺失病例配偶有妊娠丢失发生。     

516例无精症Y染色体微缺失及细胞遗传学分析

目的 探讨Y染色体微缺失和细胞遗传学分析在无精症中的相关性.方法 对2015年3月至2019年12月来广东省妇幼保健院就诊的诊断为无精症的患者进行外周血染色体G显带核型分析,运用多重定量荧光聚合酶链反应(quantitative fluorescent PCR,QF-PCR)技术检测Y染色体上的无精因子(azoospe...     

毛细管电泳用于Y染色体微缺失的研究

目的:探讨毛细管电泳在研究男性不育中特发性无精子症和射出精液严重少精子症与Y染色体无精子因子(azoospermiafactor,AZF)缺失的作用。方法:应用多重PCR技术对4例无精子症和29例严重少精子症患者的外周血细胞中Y染色体AZF所在的11.23区的15个位点进行扩增,分别用琼脂糖凝胶电泳和毛细管电泳分离扩增产物,并以6例正常生育男性和2例女性为对照。结果:毛细管电泳发现4例无精子症中3例发生缺失,29例严重少精子症患者中6例发生缺失。其中6例同为SY254(C)、SY242(C)、SY255(C)、SY239(C)、SY152(D)缺失。6例正常生育男性毛细管电泳未发现Y染色体微缺失,而凝胶电泳有2个条带模糊,难以判断。结论:毛细管电泳可提高AZF检测准确性。Y染色体AZFc/DAZ的缺失可能是引起无精子和严重少精子并造成男性不育的重要原因之一。     

无精症、少精症患者中AZF缺失的检测

目的:探讨AZF缺失与男性无精症、少精症之间的关系。方法:采用多重PCR方法,对84例汉族无精症和少精症患者的AZF区4个STS位点:AZFa亚区的sY86、AZFb亚区的sY127、AZFc亚区的sY254和sY255进行了缺失检测。用PCR-SSCP方法对其中的48例作了sY254点突变检测。并对DAZ基因在人不同组织的表达进行了研究。结果:3例无精症患者同时具有位于AZFc亚区中DAZ基因的sY254和sY255位点缺失。48例患者未见sY254有点突变。只在睾丸组织中检测到DAZ基因的表达。结论:部分汉族无精症患者可能与AZFc的缺失有关。     

Azoospermia factor and male infertility

Recently, work has shown that azoospermia factor (AZF) microdeletions result from homologous recombination between almost identical blocks in this gene region. These microdeletions in the Y chromosome are a common molecular genetic cause of spermatogenetic failure leading to male infertility. After completion of the sequencing of the Y chromosome, the classical definition of AZFa, AZFb, and AZFc was modified to five regions, namely AZFa, P5/proximal-P1, P5/distal-P1, P4/distal-P1, and AZFc, as a result of the determination of Y chromosomal structure. Moreover, partial AZFc deletions have also been reported, resulting from recombination in their sub-ampliconic identical pair sequences. These deletions are also implicated in a possible association with Y chromosome haplogroups. In this review, we address Y chromosomal complexity and the modified categories of the AZF deletions. Recognition of the association of Y deletions with male infertility has implications for the diagnosis, treatment, and genetic counseling of infertile men, in particular candidates for intracytoplasmic sperm injection.     

The genetic and cytogenetic basis of male infertility

Despite the difficulties in determining the relative maternal vs. paternal contributions to infertility it is often suggested that a male factor problem is implicated in 50% of cases. This review is concerned specifically with male fertility disorders that have a clearly defined genetic component. The genetic causes of infertility can be broken down into Y chromosome deletions (specifically deletions in the AZF a, b, and c regions), single gene disorders (particularly those relating to the CFTR gene), multifactorial causes and chromosome abnormalities. Chromosome abnormalities can be numerical (such as trisomy—full blown or mosaic) or structural (such as inversions or translocations). Of especial interest at present is the incidence of levels of numerical chromosome abnormalities in the sperm of infertile men; prospects for screening sperm for such abnormalities are discussed.     

Male infertility in China: laboratory finding for AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China

Purposes

To investigate the frequencies of AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China. Moreover, to compare the prevalence of these abnormalities with other countries and regions in the world.

Methods

305 infertile men were enrolled. A complete semen analysis and reproductive hormones were measured according to standard methods. Multiplex polymerase chain reaction (PCR) amplification using nine specific sequence-tagged sites (STS) were used to detect AZF microdeletions. Karyotype analyses were performed on peripheral blood lymphocytes with standard G-banding.

Results

Of the 305 infertile men, 28 (9.2%) had AZF microdeletions and 26 (8.5%) had chromosomal abnormalities. The most frequent microdeletions were in the AZFc+d, followed by AZFc, AZFb+c+d and AZFa. A total of 19 patients (82.6%) had Klinefelter′s syndrome (47, XXY) in the azoospermic group.

Conclusions

The freqencies of AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China were comparable with infertile men from other countries and regions. However, there was a slightly higher prevalence rate of AZF microdeletions in oligozoospermic patients than reported in previous studies.     

Management of male infertility

Male factor infertility is the commonest single reason for infertility in couples trying to have children. This article summarizes the aetiology, classification, and management of male factor infertility. The cause for male infertility can be broadly classified into pre-testicular, testicular and post testicular causes depending on the underlying pathology. A detailed history and examination are crucial alongside investigations to delineate the cause. The management for male infertility varies depending on the cause of male infertility. Treatment includes lifestyle modifications, medical management, surgical management, and surgical sperm retrieval followed by assisted reproduction.     

AZF microdeletions of the Y chromosome and in vitro fertilization outcome

OBJECTIVE: To determine whether the presence of a Y microdeletion confers any adverse effects on in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) outcome. DESIGN: Retrospective case-control study. SETTING: Academic infertility center. PATIENT(S): A total of 17 patients with Y microdeletions who attempted IVF/ICSI cycles at our center between March 1996 and March 2002 were studied. Study patients were analyzed in two groups: those who underwent testicular sperm extraction (TESE) and those for whom ejaculated sperm was used. INTERVENTION(S): The two patient study groups were matched to controls treated at the same time who had either nonobstructive severe oligozoospermia or azoospermia with normal Y chromosomes. Controls were matched for age of the female partner, sperm concentration, and number of embryos transferred. MAIN OUTCOME MEASURE(S): Fertilization and clinical pregnancy rates. RESULT(S): Sperm was only obtained from patients with azoospermic factor (AZF)c microdeletions (and from one patient with a partial AZFb microdeletion). A trend toward lower fertilization rates in patients with Y microdeletions was noted, which did not reach statistical significance. Clinical pregnancy rates per cycle and per transfer were similar to those for controls. CONCLUSION(S): Patients with AZFc microdeletions seem to have IVF/ICSI outcomes comparable to those of controls with normal Y chromosomes.