Chen Wen, Dong Li, Wei Chaofeng, Wu Haicui
First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250011, China.
Department of Reproduction and Genetics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
J Assist Reprod Genet. 2025 Feb;42(2):389-403. doi: 10.1007/s10815-024-03301-8. Epub 2024 Dec 7.
Diminished ovarian reserve (DOR) is characterized by a decrease in the number and quality of oocytes, with its incidence increasing annually. Its pathogenesis remains unclear, making it one of the most challenging problems in the field of assisted reproduction. Epigenetic modification, a molecular mechanism affecting genomic activity and expression without altering the DNA sequence, has been widely studied in reproductive medicine and has attracted considerable attention regarding DOR. This review comprehensively examines the various epigenetic regulatory changes in ovarian granulosa cells (OGCs) and oocytes during DOR. DNA methylation plays a crucial role in regulating granulosa cell function, hormone production, and oocyte development, maturation, and senescence. Histone modifications are involved in regulating follicular activation, while non-coding RNAs, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), regulate granulosa cell function and oocyte development. N6-methyladenosine (m6A) modifications are associated with age-related oocyte senescence. Epigenetic clocks based on DNA methylation show potential in predicting ovarian reserve in DOR. Furthermore, it discusses the potential for utilizing epigenetic mechanisms to better diagnose and manage DOR.
卵巢储备功能减退（DOR）的特征是卵母细胞数量和质量下降，其发病率逐年上升。其发病机制尚不清楚，这使其成为辅助生殖领域最具挑战性的问题之一。表观遗传修饰是一种在不改变DNA序列的情况下影响基因组活性和表达的分子机制，在生殖医学中已得到广泛研究，并在DOR方面引起了相当大的关注。本综述全面研究了DOR期间卵巢颗粒细胞（OGCs）和卵母细胞中各种表观遗传调控变化。DNA甲基化在调节颗粒细胞功能、激素产生以及卵母细胞发育、成熟和衰老方面起着关键作用。组蛋白修饰参与调节卵泡激活，而长链非编码RNA（lncRNAs）和微小RNA（miRNAs）等非编码RNA则调节颗粒细胞功能和卵母细胞发育。N6-甲基腺苷（m6A）修饰与年龄相关的卵母细胞衰老有关。基于DNA甲基化的表观遗传时钟在预测DOR中的卵巢储备方面显示出潜力。此外，本文还讨论了利用表观遗传机制更好地诊断和管理DOR的可能性。
