Reproductive Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China.
Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China.
Aging (Albany NY). 2021 Jun 8;13(11):15193-15213. doi: 10.18632/aging.203080.
The molecular mechanisms underlying premature ovarian failure, which seriously impacts the physical and psychological health of patients, are not fully understood. Here, we present the role of TRDMT1 in reactive oxygen species-induced granulosa cells death, which is considered an important cause of premature ovarian failure. We found that reactive oxygen species were increased in a HO dose-dependent manner and accompanied by the nuclear shuttling of TRDMT1, increased DNA damage and increased apoptosis of granulosa cells. In addition, reactive oxygen species-induced granulosa cells apoptosis could be prevented by the antioxidant N-acetylcysteine or overexpression of TRDMT1. Furthermore, DNA repair following reactive oxygen species induction was severely impaired/enhanced in TRDMT1 mutants, which exhibited reduced/increased RNA m5C methylation activity. Altogether, our results reveal a novel role of TRDMT1 in the regulation of premature ovarian failure through the repair of reactive oxygen species-triggered DNA damage in granulosa cells and provide an improved understanding of the mechanisms underlying granulosa cells apoptosis, which could potentially be useful for future clinical treatments of premature ovarian failure.
TRDMT1 通过修复活性氧诱导的颗粒细胞 DNA 损伤在卵巢早衰发生中的作用及机制研究
卵巢早衰的发病机制尚不完全清楚，严重影响患者的身心健康。本研究旨在探讨 TRDMT1 在活性氧诱导的颗粒细胞死亡中的作用及其分子机制，因为活性氧诱导的颗粒细胞死亡被认为是卵巢早衰的重要原因之一。结果发现，随着 HO 剂量的增加，活性氧的产生也随之增加，同时伴随着 TRDMT1 的核转位、DNA 损伤的增加和颗粒细胞凋亡的增加。此外，抗氧化剂 N-乙酰半胱氨酸或 TRDMT1 的过表达可以预防活性氧诱导的颗粒细胞凋亡。进一步研究发现，TRDMT1 突变体的 DNA 修复严重受损/增强，表现为 RNA m5C 甲基化活性降低/增加。综上所述，本研究揭示了 TRDMT1 通过修复活性氧诱导的颗粒细胞 DNA 损伤在卵巢早衰发生中的新作用，为进一步研究颗粒细胞凋亡的机制提供了理论依据，可能为卵巢早衰的临床治疗提供新的靶点。
