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了解子宫内膜中的表观遗传调控——来自具有着床缺陷的小鼠模型的经验教训。

Understanding epigenetic regulation in the endometrium - lessons from mouse models with implantation defects.

作者信息

Kobayashi Ryosuke, Hatada Izuho

机构信息

Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.

Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.

出版信息

Epigenomics. 2025 Jun;17(8):541-554. doi: 10.1080/17501911.2025.2491298. Epub 2025 Apr 14.

Abstract

Endometrial function, crucial for successful embryo implantation, is significantly influenced by epigenetic regulation. This review investigates the crucial roles of DNA methylation, histone modifications, chromatin remodeling, and RNA methylation in endometrial receptivity and implantation, based on a survey of recent literature on knockout mouse models with implantation defects. These models illuminate how epigenetic disruptions contribute to implantation failure, a significant human reproductive health concern. DNA methylation and histone modifications modulate endometrial receptivity by affecting gene silencing and chromatin structure, respectively. Chromatin remodeling factors also play a critical role in endometrial dynamics, influencing gene expression. Furthermore, RNA methylation emerges as critical in implantation through transcriptional and translational control. While human studies provide limited epigenetic snapshots, mouse models with suppressed epigenetic regulators reveal direct causal links between epigenetic alterations and implantation failure. Understanding these epigenetic interactions offers potential for novel therapies addressing reproductive disorders.

摘要

子宫内膜功能对胚胎成功着床至关重要,其受到表观遗传调控的显著影响。基于对近期有关具有着床缺陷的基因敲除小鼠模型文献的调查,本综述研究了DNA甲基化、组蛋白修饰、染色质重塑和RNA甲基化在子宫内膜容受性和着床中的关键作用。这些模型阐明了表观遗传破坏如何导致着床失败,这是一个重大的人类生殖健康问题。DNA甲基化和组蛋白修饰分别通过影响基因沉默和染色质结构来调节子宫内膜容受性。染色质重塑因子在子宫内膜动态变化中也起着关键作用,影响基因表达。此外,RNA甲基化通过转录和翻译控制在着床过程中至关重要。虽然人体研究提供的表观遗传快照有限,但抑制表观遗传调节因子的小鼠模型揭示了表观遗传改变与着床失败之间的直接因果关系。了解这些表观遗传相互作用为治疗生殖障碍提供了新的疗法潜力。

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