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Canxin Wen Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health,Shandong University, Jinan, Shandong, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

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Linlin Jiang Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

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Ping Pan Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

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Jia Huang Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

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Yanxin Xie Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

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Songbang Ou Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

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Yu Li Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

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In brief

Ovarian aging results in reactive oxygen species accumulation and mitochondrial deterioration. During the aging process, GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells.

Abstract

Ovarian aging critically influences reproductive potential, with a marked decrease in oocyte quality and quantity and an increase in oxidative stress and mitochondrial dysfunction. This study elucidates the role of guanine-rich RNA sequence binding factor 1 (GRSF1) in the aging of ovarian granulosa cells (GCs). We observed a significant reduction in GRSF1 within GCs correlating with patient age, utilizing clinical samples from IVF patients. Using an siRNA-mediated knockdown technique, we established that diminished GRSF1 expression exacerbates mitochondrial dysfunction, elevates reactive oxygen species, and impairs ATP production. Furthermore, RNA immunoprecipitation revealed GRSF1’s interaction with superoxide dismutase 2 (SOD2) mRNA, a key antioxidant enzyme, suggesting a mechanism whereby GRSF1 modulates oxidative stress. Downregulation of SOD2 reversed the protective effects of GRSF1 overexpression on mitochondrial function. These insights into the role of GRSF1 in ovarian aging may guide the development of interventions to improve fertility outcomes in advanced age.

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