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成熟和衰老卵母细胞中的DNA甲基化机制

DNA methylation mechanisms in the maturing and ageing oocyte.

作者信息

Caniçais Carla, Vasconcelos Sara, Santos Fátima, Dória Sofia, Marques C Joana

机构信息

Genetics Unit, Department of Pathology, Faculty of Medicine University of Porto (FMUP), Porto, 4200-319, Portugal.

ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Porto, 4050-313, Portugal.

出版信息

Epigenetics Chromatin. 2025 Jun 11;18(1):34. doi: 10.1186/s13072-025-00600-x.

Abstract

Oocyte maturation involves both nuclear and cytoplasmic processes that are critical for the acquisition of oocyte competence. Granulosa cells, surrounding the oocyte, play a pivotal role in the maturation process, with mechanisms such as cAMP signaling significantly influencing oocyte development. Epigenetic mechanisms - including DNA methylation and its oxidative derivatives, histone post-translational modifications and chromatin remodeling - interfere with the accessibility of transcription factors to regulatory regions of the genome, such as promoter regions of genes, hence generally regulating gene expression profiles; however, in oocytes, transcription is largely independent of DNA methylation patterns. Here we highlight epigenetic reprogramming events occurring during oocyte development and ageing, focusing on the establishment of gamete-specific epigenetic marks, including DNA modifications at imprinted regions, and age-related epigenetic changes. We focus on the mechanisms of DNA methylation and demethylation during mouse and human oocyte maturation, alongside an exploration of how ageing impacts the oocyte epigenome and its implications for reproductive success. By providing a comprehensive analysis of the role of epigenetics in oocyte development and maturation, this review addresses the importance of comprehending these processes to enhance in vitro fertilization treatments and improve reproductive outcomes.

摘要

卵母细胞成熟涉及细胞核和细胞质过程,这些过程对于获得卵母细胞能力至关重要。围绕卵母细胞的颗粒细胞在成熟过程中起关键作用,诸如cAMP信号传导等机制会显著影响卵母细胞发育。表观遗传机制——包括DNA甲基化及其氧化衍生物、组蛋白翻译后修饰和染色质重塑——会干扰转录因子对基因组调控区域(如基因启动子区域)的可及性,从而总体上调节基因表达谱;然而,在卵母细胞中,转录在很大程度上独立于DNA甲基化模式。在此,我们着重介绍卵母细胞发育和衰老过程中发生的表观遗传重编程事件,重点关注配子特异性表观遗传标记的建立,包括印记区域的DNA修饰以及与年龄相关的表观遗传变化。我们聚焦于小鼠和人类卵母细胞成熟过程中DNA甲基化和去甲基化的机制,同时探讨衰老如何影响卵母细胞表观基因组及其对生殖成功的影响。通过全面分析表观遗传学在卵母细胞发育和成熟中的作用,本综述阐述了理解这些过程对于加强体外受精治疗和改善生殖结局的重要性。

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