妊娠期糖尿病通过增加EZH2导致卵母细胞基因组高甲基化。

Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2.

作者信息

Guo Hong-Yan, Tang Shou-Bin, Li Li-Jun, Lin Jing, Zhang Ting-Ting, Chao Shuo, Jin Xiao-Wen, Xu Kui-Peng, Su Xiao-Feng, Yin Shen, Zhao Ming-Hui, Huang Gui-An, Yang Li-Jia, Shen Wei, Zhang Lei, Zhang Cui-Lian, Sun Qing-Yuan, Ge Zhao-Jia

机构信息

College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, People's Republic of China.

Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.

出版信息

Nat Commun. 2025 Jan 2;16(1):127. doi: 10.1038/s41467-024-55499-x.

DOI:10.1038/s41467-024-55499-x

PMID:39747080

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11696910/

Abstract

Gestational diabetes mellitus (GDM), a common pregnancy disease, has long-term negative effects on offspring health. Epigenetic changes may have important contributions to that, but the underlying mechanisms are not well understood. Here, we report the influence of GDM on DNA methylation of offspring (GDF1) oocytes and the possible mechanisms. Our results show that GDM induces genomic hyper-methylation of offspring oocytes, and at least a part of the altered methylation is inherited by F2 oocytes, which may be a reason for the inheritance of metabolic disorders. We further find that GDM exposure increases the expression of Ezh2 in oocytes. Ezh2 regulates DNA methylation via DNMT1, and Ezh2 knockdown reduces the genomic methylation level of GDF1 oocytes. These results suggest that GDM may induce oocyte genomic hyper-methylation of offspring via enhancing the Ezh2 expression recruiting more DNMT1 into nucleus.

摘要

妊娠期糖尿病（GDM）是一种常见的妊娠疾病，对后代健康有长期负面影响。表观遗传变化可能对此有重要影响，但其潜在机制尚不清楚。在此，我们报告了GDM对后代（GDF1）卵母细胞DNA甲基化的影响及其可能机制。我们的结果表明，GDM诱导后代卵母细胞基因组高甲基化，且至少部分改变的甲基化由F2卵母细胞继承，这可能是代谢紊乱遗传的一个原因。我们进一步发现，暴露于GDM会增加卵母细胞中Ezh2的表达。Ezh2通过DNMT1调节DNA甲基化，敲低Ezh2可降低GDF1卵母细胞的基因组甲基化水平。这些结果表明，GDM可能通过增强Ezh2表达，招募更多DNMT1进入细胞核，从而诱导后代卵母细胞基因组高甲基化。