ETV5 mutations: revisiting Sertoli cell only syndrome.
ETV5 mutations: revisiting Sertoli cell only syndrome.
复制标题
ETV5 突变：重温仅支持细胞综合征。
DOI：
10.1016/j.fertnstert.2012.06.047
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发表时间：
2012
影响因子：
6.7
通讯作者：
Yatsenko,AlexanderN
中科院分区：
文献类型：
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作者：
Yatsenko,AlexanderN
尽管不孕不育在人类社会中发病率高，历史悠久，但在某种程度上，它仍然是一种神秘的健康状况。自然，精子密度低、精子活力低、精子形态不佳等精子缺陷与生育能力下降有关。然而，正常的精液参数并不能保证正常生育。在精液缺陷中，无精子症(精液中没有生殖细胞)和仅支持细胞综合征(SCOS，精液和睾丸中没有生殖细胞，也称为生精衰竭)是最严重的病理情况。目前，遗传因素被认为在男性因素不育中起着重要作用(1)。然而，多年来，医学和公众普遍认为，染色体异常和Y染色体微缺失是无精子症和少精子症的主要原因(2，3)。尽管这是毋庸置疑的，但各自的基因测试只能在男科诊所看到的一小部分患者中识别出这些缺陷。其余大多数患者有男性因素不育症的描述性或特发性诊断。尽管有许多尝试和丰富的动物男性不育模型(4)，但对特发性男性因素不育患者中无精子症和SCOS的遗传基础知之甚少。O‘Bryan博士和他的同事在《生育与不育杂志》上发表的文章《可生育和不育男性非梗阻性无精子症与仅支持细胞综合征相关的ETV5基因中的遗传变异》中提出了少数成功的揭示SCOS遗传原因的尝试之一(5)。在这篇文章中，奥布莱恩博士和他的同事们展示了人类翻译研究整体方法的一个很好的例子。他们精心挑选了SCOS临床表型的患者，并成功收集了足够数量的无精子症和SCOS患者。基于SCOS和男性因素不育的小鼠同源基因敲除模型(6)，ETV5被精心选择为合理的候选基因。产生了一种抗人ETV5蛋白的抗体，这些抗体共同提供了有价值的证据，表明该蛋白在人类睾丸组织中有显著表达，并且对精子发生具有重要意义。最后，他们进行了一项出色的遗传学研究，通过桑格DNA测序在相当大的无精子症患者和生育对照人群中筛选出所有外显子和两侧内含子区域的DNA变化。尽管这篇文章只报道了一小部分ETV5突变的无精子症患者，但考虑到有数百个重要基因在人类精子发生的不同阶段表达或控制成熟精子的男性生殖功能，这一结果并不令人惊讶。一
Infertility, despite its high incidence and long history in human society, is still somewhat of a mysterious health condition. Naturally, semen defects like low sperm concentration, low sperm motility, and poor sperm morphology are associated with reduced fertility. However, normal semen parameters are not a guarantee for normal fertility. Among semen defects, azoospermia (absence of germ cells in the semen) and Sertoli cell only syndrome (SCOS, absence of germ cells in the semen and testis, also known as Spermatogenic Failure) are the most serious pathological conditions. Currently, genetic factors are considered to play an important role in male factor infertility (1). However, for many years the medical and general public perception was that chromosomal aberrations and Y-chromosome microdeletions were mainly responsible for azoospermia and oligozoospermia (2, 3). Although it is not disputable, respective genetic testing could only identify those defects in a small proportion of patients seen in the andrology clinic. The remaining majority of patients have descriptive or idiopathic diagnoses of male factor infertility. Despite many attempts and a wealth of animal male infertility models (4), little is known about the genetic basis of azoospermia and SCOS in patients with idiopathic male factor infertility.One of the few successful attempts to reveal the genetic cause of SCOS is presented by Dr. O'Bryan and colleagues in the article ‘‘Genetic variants in the ETV5 gene in fertile and infertile men with non-obstructive azoospermia associated with Sertoli cell only syndrome’’in the Fertility and Sterility journal (5). In the article, Dr. O'Bryan and colleagues demonstrated a great example of an integral approach to human translational studies. They performed a thoughtful selection of patients with SCOS clinical phenotype and successfully collected a sufficient number of patients with azoospermia and SCOS. ETV5 was carefully selected as a plausible gene-candidate based on the mouse orthologue knockout model with SCOS and male factor infertility (6). An antibody against human ETV5 protein was generated, which collectively provided valuable evidence that the protein has significant expression in human testis tissue and is important for spermatogenesis. Finally, they carried out an excellent genetic investigation screening of DNA alterations in all exons and flanking intronic regions by Sanger DNA sequencing in a fairly large population of azoospermic patients and fertile controls. Although the article reports only a small proportion of azoospermic patients with ETV5 mutations, this outcome is not surprising, considering that there are hundreds of important genes that are expressed during various stages of human spermatogenesis or control the male reproductive function of mature spermatozoa. One