Lin Yi-Nan, Matzuk Martin M
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Methods Mol Biol. 2014;1154:25-37. doi: 10.1007/978-1-4939-0659-8_2.
Early in embryogenesis, cells that are destined to become germ cells take on a different destiny from other cells in the embryo. The germ cells are not programmed to perform "vital" functions but to perpetuate the species through the transfer of genetic materials to the next generation. To fulfill their destiny, male germ cells undergo meiosis and extensive morphogenesis that transforms the round-shaped cells into freely motile sperm propelled by a beating flagellum to seek out their missing half. Apparently, extra genes and additional regulatory mechanisms are required to achieve all these unique features, and an estimated 11 % of genes are involved in fertility in Drosophila (Hackstein et al., Trends Genet 16(12):565-572, 2000). If comparative numbers of male fertility genes are needed in mammals, extra risks of male fertility problems are associated with disruptive mutations in those genes. Among human male infertility cases, approximately 22 % were classified as "idiopathic," a term used to describe diseases of unknown causes, with idiopathic oligozoospermia being the most common semen abnormality (11.2 %) (Comhaire et al., Int J Androl (Suppl 7):1-53, 1987). "Idiopathic" is a widely used adjective that is used to reflect our lack of understanding of the genetics of male fertility. Fortunately, after more than two decades of phenotypic studies using knockout mice and identifying genes disrupted in spontaneous mutant mice, we have unveiled new and unexpected aspects of crucial gene functions for fertility. Other efforts to categorize genes involved in male fertility in mammals have suggested a total of 1,188 genes (Hermo et al., Microsc Res Tech 73(4):241-494, 2010). Although intracytoplasmic sperm injection (ICSI) can be used to bypass many fertilization obstacles to achieve fertilization with only a few extracted sperm, the widespread use of ICSI without proper knowledge for genetic testing and counseling could still potentially propagate pleiotropic gene mutations associated with male infertility and other genetic diseases (Alukal and Lamb, Urol Clin North Am 35(2):277-288, 2008). In this chapter, we give a brief account of major events during the development of male germ cells and focus on the functions of several crucial genes that have been studied in mutant mouse models and are potential causes of human male infertility.
在胚胎发育早期，注定要成为生殖细胞的细胞走上了与胚胎中其他细胞不同的命运之路。生殖细胞并非被设定去执行“维持生命”的功能，而是通过将遗传物质传递给下一代来延续物种。为了完成其使命，雄性生殖细胞经历减数分裂和广泛的形态发生过程，将圆形细胞转变为由摆动的鞭毛推动的自由游动精子，去寻找它们缺失的另一半。显然，实现所有这些独特特征需要额外的基因和额外的调控机制，据估计在果蝇中有11%的基因与生育力有关（哈克斯坦等人，《遗传学趋势》16(12):565 - 572，2000年）。如果哺乳动物也需要类似数量的雄性生育力基因，那么这些基因发生破坏性突变会带来额外的雄性生育问题风险。在人类男性不育病例中，约22%被归类为“特发性”，这一术语用于描述病因不明的疾病，特发性少精子症是最常见的精液异常（11.2%）（科迈尔等人，《国际男性学杂志》（增刊7）:1 - 53，1987年）。“特发性”是一个广泛使用的形容词，用于反映我们对男性生育遗传学的缺乏了解。幸运的是，经过二十多年使用基因敲除小鼠的表型研究以及鉴定自发突变小鼠中被破坏的基因，我们揭示了生育力关键基因功能的新的和意想不到的方面。其他对哺乳动物中涉及雄性生育力的基因进行分类的研究表明共有1188个基因（埃尔莫等人，《显微镜研究与技术》73(4):241 - 494，2010年）。尽管卵胞浆内单精子注射（ICSI）可用于绕过许多受精障碍，仅用少量提取的精子实现受精，但在没有进行适当的基因检测和咨询的情况下广泛使用ICSI仍可能潜在地传播与男性不育和其他遗传疾病相关的多效基因突变（阿卢卡尔和兰姆，《北美泌尿外科临床杂志》35(2):277 - 288，2008年）。在本章中，我们简要介绍雄性生殖细胞发育过程中的主要事件，并重点关注在突变小鼠模型中已被研究且可能是人类男性不育潜在原因的几个关键基因的功能。
