Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P.R. China.
Int J Biol Sci. 2022 May 16;18(9):3592-3604. doi: 10.7150/ijbs.69771. eCollection 2022.
Gamete abnormalities and reproductive system tumors have become a dominant cause of infertility, troubling people globally. In recent years, increasing evidence emerged and found that N6-methyladenosine (m6A) played a leading role in reproduction. The biological effects of m6A modification are dynamically and reversibly regulated by methyltransferases (writers), WTAP, METTL3, METTL14 and KIAA1429, demethylases (erasers), FTO and ALKBH5, and m6A binding proteins (readers), including YTH domain. In this review, we highlight the change of m6A modification in abnormal oogenesis, female reproductive system diseases including reproductive system tumors, adenomyosis, endometriosis, premature ovarian failure and polycystic ovary syndrome. Moreover, we review some of the mechanisms and the specific modified genes that have been identified. Especially, with the underlying mechanisms being uncovered, m6A and its protein machineries are expected to be the markers and targets for the diagnosis and treatment of female reproductive dysfunction.
配子异常和生殖系统肿瘤已成为不孕的主要原因，困扰着全球的人们。近年来，越来越多的证据表明，N6-甲基腺苷（m6A）在生殖中起主导作用。m6A 修饰的生物学效应通过甲基转移酶（writer）、WTAP、METTL3、METTL14 和 KIAA1429、去甲基化酶（eraser）、FTO 和 ALKBH5 以及 m6A 结合蛋白（reader），包括 YTH 结构域，进行动态和可逆调节。在这篇综述中，我们强调了 m6A 修饰在异常卵发生、女性生殖系统疾病包括生殖系统肿瘤、腺肌病、子宫内膜异位症、卵巢早衰和多囊卵巢综合征中的变化。此外，我们还回顾了一些已经确定的机制和特定的修饰基因。特别是，随着潜在机制的揭示，m6A 及其蛋白机器有望成为女性生殖功能障碍诊断和治疗的标志物和靶点。
