Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm.
Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm.
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广泛的表观遗传异常表明，人类精子异常的DNA甲基化缺陷。
DOI：
10.1371/journal.pone.0001289
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发表时间：
2007-12-12
期刊：
影响因子：
3.7
通讯作者：
Sokol RZ
中科院分区：
文献类型：
--
作者：
Houshdaran S;Cortessis VK;Siegmund K;Yang A;Laird PW;Sokol RZ
男性因素不孕是一种常见的情况，病因不明的情况下，一个高比例。生殖系的异常表观遗传编程被认为是目前诊断为特发性不育的一些男性精子发生受损的可能机制。在生殖细胞成熟和配子发生期间，生殖系细胞经历广泛的表观遗传重编程。这一过程涉及广泛擦除DNA甲基化的体细胞样模式，然后通过从头DNA甲基化建立性别特异性模式。从理论上讲，男性生殖细胞系的不完全重编程可能导致精子DNA甲基化改变和精子发生受损。我们测定了参加不育诊所的夫妇的男性成员收集的精液样本中精子的浓度、活力和形态。使用MethyLight和Illumina分析，我们测量了从相同样品的纯化精子中分离的DNA的甲基化。低质量精子的DNA中，许多序列的甲基化水平升高。这是第一个广泛的表观遗传缺陷与异常精液参数的报告。我们的研究结果表明，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甲基化的不当删除。
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. 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.
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影响因子：
4.8
作者：
Chang, Hung-Shu;Anway, Matthew D.;Skinner, Michael K.
通讯作者：
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影响因子：
6.1
作者：
Benchaib, M;Braun, V;Guérin, JF
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DOI：
10.2307/2991524
发表时间：
1998-01-01
期刊：
FAMILY PLANNING PERSPECTIVES
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作者：
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作者：
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作者：
ARIEL, M;CEDAR, H;MCCARREY, J
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MCCARREY, J