Research Paper Volume 13, Issue 11 pp 15193—15213
TRDMT1 participates in the DNA damage repair of granulosa cells in premature ovarian failure
- 1 Reproductive Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China
- 2 Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China
- 3 Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China
- 4 International Genome Center, Jiangsu University, Zhenjiang 212013, Jiangsu, China
Received: November 20, 2020 Accepted: February 16, 2021 Published: June 8, 2021
https://doi.org/10.18632/aging.203080How to Cite
Copyright: © 2021 Sha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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 H2O2 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.