FTO protects human granulosa cells from chemotherapy-induced cytotoxicity

Reproductive Biology and Endocrinology

Wei Wang¹  Nini Zheng²  Linnan Yuan²  Feiyan Cheng²  Xin Guan²  Xinyuan Yang²  Lijun Wang²  Rongli Wang² 

[1] Department of Anesthesiology, the First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, China;Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, China;

关键词: FTO;    POF;    Menstrual-derived stem cells;    BNIP3;   

DOI  :  10.1186/s12958-022-00911-8

来源: Springer

【 摘 要 】

BackgroundPremature ovarian failure (POF) is a serious problem for young women who receive chemotherapy, and its pathophysiological basis is the dysfunction of granulosa cells. According to previous reports, menstrual-derived stem cells (MenSCs) can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF. Fat mass- and obesity-associated (FTO) was reported to be associated with oocyte development and maturation. FTO was decreased in POF and may be a biomarker for the occurrence of POF. Knockdown of FTO in granulosa cells promoted cell apoptosis and inhibited proliferation. But the relationship between FTO and ovarian repair was still unclear. This study was aimed at investigating the FTO expression level and the role of FTO in the MenSCs recovering the function of injured granulosa cells.MethodFirst, cisplatin was used to establish a granulosa cell injury model. Then, the MenSCs and injured granulosa cell coculture model and POF mouse model were established in this study to explore the role of FTO. Furthermore, gain- and loss-of-function studies, small interfering RNA transfection, and meclofenamic acid (MA), a highly selective inhibitor of FTO, studies were also conducted to clarify the regulatory mechanism of FTO in granulosa cells.ResultsMenSCs coculture could improve the function of injured granulosa cells by increasing the expression of FTO. MenSCs transplantation restored the expression of FTO in the ovaries of POF mice. Overexpression of FTO restored the injured cell proliferation and decreased apoptosis by regulating the expression of BNIP3. Down-regulation of FTO got the opposite results.ConclusionsIn the treatment of MenSCs, FTO has a protective effect, which could improve the viability of granulosa cells after cisplatin treatment by decreasing the expression of BNIP3. Meanwhile, FTO may provide new insight into therapeutic targets for the chemotherapy-induced POF.

【 授权许可】

CC BY