Effects of obesity on DNA methylation and DNA methyltransferases in the reproductive system

肥胖对生殖系统中DNA甲基化和DNA甲基转移酶的影响

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Abstract

Obesity is increasingly recognized as a condition with profound systemic and epigenetic consequences. However, the molecular mechanisms linking obesity to reproductive dysfunction remain incompletely understood. Accumulating evidence suggests that epigenetic regulation, particularly DNA methylation, contributes to and is modified by obesity, thereby influencing gene expression in gonadal tissues and germ cells. DNA methylation is essential for normal oogenesis and spermatogenesis and is mediated by DNA methyltransferases (DNMTs), whose expression and activity are tightly regulated throughout germ cell development. This review synthesizes current experimental and clinical evidence regarding obesity-associated alterations in DNMT expression and DNA methylation patterns across female and male reproductive systems and examines how these epigenetic disruptions contribute to infertility. Obesity is most frequently associated with a hypermethylated epigenetic landscape in female reproductive tissues, whereas the male germline more commonly exhibits global or locus-specific hypomethylation, reflecting sex-specific epigenetic responses to metabolic stress. Studies spanning ovarian tissue, oocytes, sperm, and early embryos demonstrate that obesity-induced DNMT dysregulation and DNA methylation remodeling disrupt transcriptional programs governing folliculogenesis, spermatogenesis, and embryo development.

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