TRDMT1 Participates in the DNA Damage Repair of Granulosa Cells in Premature Ovarian Failure

The molecular mechanisms of premature ovarian failure (POF), which seriously impacts the physical and psychological health of patients, are not been fully understood. Here, we present the role of TRDMT1 in reactive oxygen species (ROS)-induced granulosa cells (GCs) death, which is considered to be an important cause of POF. We found that ROS were increased in a H2O2 dose-dependent manner and were accompanied by nuclear shuttling of TRDMT1, increased DNA damage and increased apoptosis in GCs. In addition, ROS-induced GCs apoptosis could be prevented by antioxidant N-acetylcysteine (NAC) or overexpression of TRDMT1. Furthermore, DNA repair following ROS induction was severely impaired/enhanced in the TRDMT1 mutant that exhibited reduced/increased RNA m5C methylation activity. Taken together, our results propose a novel role for TRDMT1 in regulating POF through the repair of ROS-triggered DNA damage in GCs, and they provide improved understanding of the mechanisms underlying GCs apoptosis, which could potentially be useful for future clinical treatment of POF. Funding Statement: This research was supported by Natural Science Foundation of China (Grant No. 81672913/81871343), Social Develop ment Project of Jiangsu (Grant No. BE2018693/BE2017698), Natural Science Foundation of Jiangsu Province (BK20181 226), Jiangsu Provincial Medical Youth Talent (QNRC2016460, FRC201788). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: All Clinical research were performed with the approval of the Jiangsu University Ethics Committee, and informed consent was obtained from all patients. All the animal experiments were manipulated according to guidelines approved by the Jiangsu University Medical Experimental Animal Care Commission.