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精子表观基因组及其对胚胎发育的潜在影响。

The sperm epigenome and potential implications for the developing embryo.

机构信息

Andrology and IVF Laboratories, Department of Surgery, University of Utah School of Medicine, 675 Arapeen Drive, Suite 205, Salt Lake City,Utah 801-581-3740, USA.

出版信息

Reproduction. 2012 Jun;143(6):727-34. doi: 10.1530/REP-11-0450. Epub 2012 Apr 11.

Abstract

Recent work in the field of male fertility has yielded significant increases in our understanding of the sperm epigenome and its potential role in embryonic development. These new findings have enabled a broad classification of a normal epigenetic state in the male gamete and have provided insight into the possible etiologies of some idiopathic male infertility cases. Histone retention and modification, protamine incorporation into the chromatin, DNA methylation, and spermatozoal RNA transcripts appear to play important roles in the epigenetic state of mature sperm. These epigenetic factors may reveal a historical record of spermatogenesis, portend future functions in embryogenesis, and help to elucidate mechanism of pluripotency. In contrast to the once held dogma regarding the importance of the paternal epigenome, the unique epigenetic landscape in sperm appears to serve more than the gamete itself and is likely influential in the developing embryo. In fact, growing evidence suggests that mature sperm provide appropriate epigenetic marks that drive specific genes toward activation and contribute to the pluripotent state of the embryonic cells. Although not definitive, the current literature provides evidence for the role of the sperm epigenome in the embryo. Future work must be focused on the characterization of epigenetic abnormalities commonly found in individuals with compromised fertility to further establish this role. Additionally, studies should target the effects of environment and aging on the sperm epigenetic program and subsequent fertility loss to determine the etiology of aberrant epigenetic profiles.

摘要

近年来,男性生育领域的研究工作极大地增进了我们对精子表观基因组及其在胚胎发育中潜在作用的理解。这些新发现使我们能够对精子的正常表观遗传状态进行广泛分类,并深入了解一些特发性男性不育病例的可能病因。组蛋白保留和修饰、鱼精蛋白整合到染色质中、DNA 甲基化和精子 RNA 转录本似乎在成熟精子的表观遗传状态中发挥重要作用。这些表观遗传因素可能揭示了精子发生的历史记录,预示着胚胎发生中的未来功能,并有助于阐明多能性的机制。与曾经关于父系表观基因组重要性的教条相反,精子中独特的表观遗传景观似乎不仅仅为配子本身服务,而且可能对发育中的胚胎有影响。事实上,越来越多的证据表明,成熟精子提供了适当的表观遗传标记,促使特定基因激活,并有助于胚胎细胞的多能状态。尽管还不确定,但目前的文献提供了证据表明精子表观基因组在胚胎中起作用。未来的工作必须集中在描述在生育能力受损的个体中常见的表观遗传异常,以进一步确立这一作用。此外,研究还应针对环境和衰老对精子表观遗传程序以及随后生育能力丧失的影响进行研究,以确定异常表观遗传谱的病因。

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