Houshdaran Sahar, Cortessis Victoria K, Siegmund Kimberly, Yang Allen, Laird Peter W, Sokol Rebecca Z
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
PLoS One. 2007 Dec 12;2(12):e1289. doi: 10.1371/journal.pone.0001289.
Male-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive epigenetic reprogramming. This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation. Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis.
METHODOLOGY/PRINCIPAL FINDING: We determined concentration, motility and morphology of sperm in semen samples collected by male members of couples attending an infertility clinic. Using MethyLight and Illumina assays we measured methylation of DNA isolated from purified sperm from the same samples. Methylation at numerous sequences was elevated in DNA from poor quality sperm.
This is the first report of a broad epigenetic defect associated with abnormal semen parameters. Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.
男性因素导致的不育是一种常见病症，很大一部分病例的病因不明。生殖细胞的异常表观遗传编程被认为是一种可能的机制，会损害一些目前被诊断为特发性不育症男性的精子发生过程。在生殖细胞成熟和配子发生过程中，生殖系细胞会经历广泛的表观遗传重编程。这个过程包括广泛擦除类似体细胞的DNA甲基化模式，随后通过从头DNA甲基化建立性别特异性模式。理论上，男性生殖系的不完全重编程可能导致精子DNA甲基化改变以及精子发生受损。
方法/主要发现：我们测定了到不孕不育门诊就诊的夫妇中男性成员所采集精液样本中精子的浓度、活力和形态。使用甲基化荧光定量聚合酶链反应（MethyLight）和Illumina检测法，我们测量了从相同样本中纯化精子分离出的DNA的甲基化情况。在质量较差的精子的DNA中，许多序列的甲基化水平升高。
这是第一份关于与异常精液参数相关的广泛表观遗传缺陷的报告。我们的结果表明，这些表观遗传变化的潜在机制可能是男性生殖系表观遗传重编程过程中DNA甲基化擦除不当。
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