Y染色体AZF区遗传学研究进展

Y染色体无精子症因子（azoospermia factor,AZF）区域微缺失与男性不育密切相关,是最常见的导致无精子症与严重少精子症的分子遗传病因。AZF区域包括三个遗传域AZFa区,AZFb区和AZFc区。在本文中将对AZF基因结构和功能作一综述。     

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.     

1324例少精子症和无精子症患者的染色体核型分析

目的：探索男性不育中少精子症和无精子症患者的遗传异常情况,为临床诊治和咨询奠定基础。方法：回顾性分析2015年1月至2016年5月在吉林大学第二医院生殖中心男科就诊的不育患者,排除不良育产史的患者,其中少精子症876例、无精子症448例,计1 324例患者纳入研究。患者进行体格检查、彩超检查、精浆Zn测定、内分泌激素测定、染色体核型分析检测、Y染色体微缺失检测。结果：在876例少精子症患者中有78例存在染色体结构和数目异常,其中性染色体数目异常者22例,性染色体和常染色体结构异常者56例;在448例无精子症患者中有91例染色体结构和数目异常,其中性染色体数量异常者78例,结构异常者13例。此外,全部1 324例患者中染色体多态改变的有137例,无精子因子(azoospermia factor, AZF)基因微缺失的有43例。结论：男性不育少精子症和无精子症患者染色体核型异常的发生率较高,对其进行染色体核型分析有助于对病因的诊断以及遗传咨询。     

Single‐nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell‐only syndrome

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, ten novel genes involved in human spermatogenesis, including human LRWD1, have been identified by expression microarray analysis of human testictissue. The human LRWD1 protein mediates the origin recognition complex in chromatin, which is critical for the initiation of pre‐replication complex assembly in G1 and chromatin organization in post‐G1 cells. The Lrwd1 gene expression is specific to the testis in mice. Therefore, we hypothesized that mutation or polymorphisms of LRWD1 participate in male infertility, especially azoospermia. To investigate whether LRWD1 gene defects are associated with azoospermia caused by SCOS and meiotic arrest (MA), mutational analysis was performed in 100 and 30 Japanese patients by direct sequencing of the coding regions, respectively. Statistical analysis was performed for patients with SCOS and MA and in 100 healthy control men. No mutations were found in LRWD1; however, three coding single‐nucleotide polymorphisms (SNP1‐SNP3) could be detected in the patients. The genotype and allele frequencies in SNP1 and SNP2 were notably higher in the SCOS group than in the control group (P < 0.05). These results suggest the critical role of LRWD1 in human spermatogenesis.     

Are human male patients with DAX1/NR0B1 mutations infertile?

DAX-1 stands for Dosage sensitive sex-reversal, Adrenal hypoplasia congenital (AHC), on the X chromosome. DAX-1 mutations usually cause primary adrenal insufficiency or congenital adrenal hypoplasia in early childhood and hypogonadotropic hypogonadism (MIM # 300200). DAX-1 protein is necessary to maintain normal spermatogenesis. In humans, male fertility has been studied in few patients carrying DAX-1 mutations. Cases of azoospermia have been reported, as well as unsuccessful gonadotropin treatments. The clinician should be informed that TESE–ICSI technique carries a potential hope to father non-affected children, as shown in this review.     

Sertoli cell-only syndrome: etiology and clinical management

Almost 50% of infertility cases are due to male factors, and spermatogenesis failure is one of the most severe forms of male infertility. Sertoli cell-only syndrome (SCOS) also known as germ cell aplasia is characterized by azoospermia in which the seminiferous tubules of testicular biopsy are lined only with Sertoli cells. The definitive diagnosis of SCOS is by diagnostic testicular biopsy. Although SCOS may be a result of Klinefelter syndrome, most of the SCOS men have a normal karyotype. Along with genetic aberrations, signaling pathways and endocrine processes might be major factors in the development of SCOS. Sperm retrieval and intracytoplasmic sperm injection (ICSI) are available treatments for SCOS. However, some SCOS patients do not have therapeutic options to help them having a biological child. This review aims to summarize our present knowledge about SCOS and to highlight the importance of future researches in the diagnosis and treatment of this disorder.     

无精子症患者配偶性生活质量的探讨

目的探讨无精子症患者配偶的性生活质量。方法选择自愿接受性生活质量问卷调查的64例不孕女性,按其男方精液质量进行分组,无精子症组28例为研究组,精液正常因输卵管因素就诊者36例为对照组,调查2组配偶性生活质量及男性性功能状况。结果64例女性性生活质量与职业及文化程度无关,无精子症组配偶性生活总体满意度、同房时间低于对照组,差异有统计学意义（P〈0.05）;同房频率、性冷淡发生率高于对照组,差异有统计学意义（P〈0．05）。结论无精子症患者配偶性生活满意度相对较低,应积极改善不孕不育患者性心理状况。     

不同来源的精子行ICSI妊娠结局分析

目的 对少弱畸精子症患者精液精子、梗阻性无精子症(OA)患者睾丸精子和非梗阻性无精子症(NOA)患者睾丸精子行ICSI,观察3种不同来源精子的受精率、种植率和妊娠率.OA和NOA患者均采用睾丸精子抽吸术获取睾丸精子.方法 本文回顾了本院2007至2010年就诊的934对夫妇行ICSI,包括用精液精子ICSI 619对夫妇,OA 268对夫妇,NOA 47对夫妇.3组分别有569对、237对和42对夫妇进行胚胎移植.结果 重度少弱畸精子症、OA和NOA组的男女双方年龄、Gn平均用量和平均成熟卵泡数无明显差异.少弱畸精子症和OA组平均正常受精卵子数和种植率,两组的临床妊娠率也没有明显差异.NOA组正常受精卵子数和种植率与少弱畸精子症和OA组均有明显差异.在三组移植胚胎数没有差异的情况下,NOA组的临床妊娠率也明显低于少弱畸精子症和OA组.结论 本文说明非梗阻性无精子症患者睾丸精子行ICSI的受精率、种植率和临床妊娠率劣于精液精子和梗阻性无精子症患者睾丸精子.     

基于芯片微阵列数据库对无精子症相关基因挖掘及生物信息学分析

目的从分子水平探讨非梗阻性无精子症的发病机制,为临床诊疗提供新思路。 方法从基因表达综合数据库（GEO）中下载人非梗阻性无精子症的相关基因芯片数据,使用R语言对其进行归一化处理并筛选差异表达基因;使用DAVID及KEGG数据库对其进行差异基因本体功能及信号通路富集分析;通过Cytoscape绘制差异基因共表达网络并使用CytoHubba插件计算筛选核心基因（hub基因）;最后使用ClueGo及Centiscape对核心基因进行富集分析。 结果R语言筛选出518个差异表达基因,其中上调基因271个、下调基因247个;本体功能及信号通路富集分析结果提示这些差异基因在精子发生、精子染色质凝聚、精子顶体膜及囊泡形成、精卵细胞识别、细胞分化、ATP偶联及转录因子结合等生物学过程中发挥重要作用;差异基因共表达网络分析发现GAPDHS,PCSK4,TSSK1B,TSSK2等hub基因在精子发生及分化过程中发挥关键作用。 结论通过多维度挖掘GEO基因芯片数据并系统分析其内在信息,对明确非梗阻性无精子症发病的分子机制具有重要意义。     

显微外科技术在男性不育症治疗中的应用及疗效分析

目的 探讨显微外科技术在男性不育症治疗中的应用及疗效. 方法 回顾性分析2007年3月至2012年3月853例接受显微外科治疗的不育男性患者资料.其中精索静脉曲张的少弱精子症患者344例,均在硬膜外或全麻下接受精索静脉曲张显微结扎术.梗阻性无精子症患者252例,接受输精管-输精管显微吻合术60例,其中45例有双侧输精管结扎史,15例有双侧疝气手术史;其他192例接受输精管-附睾管显微吻合术.非梗阻性无精子症患者257例,均在全麻下接受睾丸显微取精术,并行病理检查.患者术后门诊随访1～12个月,随访内容为手术并发症、精液参数及女方妊娠情况. 结果 ①344例精索静脉曲张患者术后3个月复查精液,术前精子密度为(10±6)×106/ml,前向运动精子比率为(16±9)％,术后精子密度为(15 ±8)×106/ml,前向运动精子比率为(28±14)％,48.8％(168/344)的患者术后精液质量提高,10.8％ (37/344)的患者配偶自然受孕.②输精管输精管显微吻合术共60例,总复通率为80.0％ (48/60),妊娠率为35.0％ (21/60).192例接受输精管附睾管显微吻合术,复通率为53.1％(102/192),妊娠率为19.8％ (38/192).③257例非梗阻性无精子症患者睾丸活检精子检出率为38.1％(98/257),显微取精法精子获取率为60.3％(155/257),显著性高于活检术(P＜0.01).仅2例患者出现阴囊血肿,经清创换药处理后治愈. 结论 显微外科技术治疗男性不育症可有效改善和恢复男性生育力,创伤小,降低医疗费用,符合生殖伦理.