Andrology and IVF Laboratories, Department of Surgery, University of Utah, Salt Lake City, UT 84108, USA.
Asian J Androl. 2011 Jan;13(1):76-80. doi: 10.1038/aja.2010.61. Epub 2010 Oct 25.
The scope of paternal contributions during early embryonic development has long been considered limited. Dramatic changes in chromatin structure throughout spermatogenesis have been thought to leave the sperm void of complex layers of epigenetic regulation over the DNA blueprint, thus leaving the balance of that regulation to the oocyte. However, recent work in the fields of epigenetics and male factor infertility has placed this long-held, and now controversial dogma, in a new light. Elegant studies investigating chromatin and epigenetic modifications in the developing sperm cell have provided new insights that may establish a more critical role for the paternal epigenome in the developing embryo. DNA methylation, histone tail modifications, targeted histone retention and protamine incorporation into the chromatin have great influence in the developing sperm cell. Perturbations in the establishment and/or maintenance of any of these epigenetic marks have been demonstrated to affect fertility status, ranging in severity from mild to catastrophic. Sperm require this myriad of chromatin structural changes not only to serve a protective role to DNA throughout spermatogenesis and future delivery to the egg, but also, it appears, to contribute to the developmental program of the future embryo. This review will focus on our current understanding of the epigenetics of sperm. We will discuss sperm-specific chromatin modifications that result in genes essential to development being poised for activation early in embryonic development, the disruption of which may result in reduced fecundity.
长期以来,人们一直认为父本在早期胚胎发育过程中的贡献有限。在精子发生过程中,染色质结构的剧烈变化被认为使精子缺乏对 DNA 蓝图的复杂层叠的表观遗传调控,从而将这种调控的平衡留给卵子。然而,表观遗传学和男性因素不育领域的最新研究成果使这一长期以来存在的、现在颇具争议的教条有了新的认识。研究精细胞中染色质和表观遗传修饰的优雅研究提供了新的见解,这些见解可能确立了父本表观基因组在胚胎发育中的更关键作用。DNA 甲基化、组蛋白尾部修饰、靶向组蛋白保留和鱼精蛋白掺入染色质对发育中的精子细胞有很大影响。已经证明,这些表观遗传标记的建立和/或维持的任何干扰都会影响生育能力,严重程度从轻度到灾难性不等。精子不仅需要这种无数的染色质结构变化来在精子发生过程中保护 DNA,并在未来输送到卵子,而且似乎还为未来胚胎的发育计划做出贡献。这篇综述将集中讨论我们目前对精子表观遗传学的理解。我们将讨论导致发育所必需的基因处于激活状态的精子特异性染色质修饰,这些修饰的破坏可能导致生育能力下降。