Sun Xiaoyan, Lu Jiafeng, Li Hong, Huang Boxian
State Key Laboratory of Reproductive Medicine, Gusu School, Suzhou Municipal Hospital, Suzhou Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Suzhou, China.
Front Cell Dev Biol. 2022 May 30;10:884295. doi: 10.3389/fcell.2022.884295. eCollection 2022.
The growth and maturation of oocyte is accompanied by the accumulation of abundant RNAs and posttranscriptional regulation. N6-methyladenosine (mA) is the most prevalent epigenetic modification in mRNA, and precisely regulates the RNA metabolism as well as gene expression in diverse physiological processes. Recent studies showed that mA modification and regulators were essential for the process of ovarian development and its aberrant manifestation could result in ovarian aging. Moreover, the specific deficiency of mA regulators caused oocyte maturation disorder and female infertility with defective meiotic initiation, subsequently the oocyte failed to undergo germinal vesicle breakdown and consequently lost the ability to resume meiosis by disrupting spindle organization as well as chromosome alignment. Accumulating evidence showed that dysregulated mA modification contributed to ovarian diseases including polycystic ovarian syndrome (PCOS), primary ovarian insufficiency (POI), ovarian aging and other ovarian function disorders. However, the complex and subtle mechanism of mA modification involved in female reproduction and fertility is still unknown. In this review, we have summarized the current findings of the RNA mA modification and its regulators in ovarian life cycle and female ovarian diseases. And we also discussed the role and potential clinical application of the RNA mA modification in promoting oocyte maturation and delaying the reproduction aging.
卵母细胞的生长和成熟伴随着大量RNA的积累和转录后调控。N6-甲基腺苷（m6A）是mRNA中最普遍的表观遗传修饰，在多种生理过程中精确调控RNA代谢以及基因表达。最近的研究表明，m6A修饰及其调控因子对卵巢发育过程至关重要，其异常表现可能导致卵巢衰老。此外，m6A调控因子的特异性缺陷会导致卵母细胞成熟障碍和女性不孕，减数分裂起始存在缺陷，随后卵母细胞无法经历生发泡破裂，最终因纺锤体组织和染色体排列紊乱而失去恢复减数分裂的能力。越来越多的证据表明，m6A修饰失调会导致包括多囊卵巢综合征（PCOS）、原发性卵巢功能不全（POI）、卵巢衰老和其他卵巢功能障碍在内的卵巢疾病。然而，m6A修饰参与女性生殖和生育的复杂而微妙的机制仍不清楚。在这篇综述中，我们总结了RNA m6A修饰及其调控因子在卵巢生命周期和女性卵巢疾病中的当前研究结果。我们还讨论了RNA m6A修饰在促进卵母细胞成熟和延缓生殖衰老方面的作用及潜在临床应用。
