Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome

Frontiers in Cell and Developmental Biology

Qiuju Chen¹  Lihua Sun²  Hui Tian³  Songguo Xue³  Caixia Zhang³  Hongjuan Ye³  Xue Xue³  Yu Liu³  Rongxiang Wang³  Shaorong Gao⁴ 

[1] Department of Assisted Reproduction, Shanghai Ninth Peoples Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;Department of Reproductive Medicine Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China;Department of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China;Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China;

关键词: polycystic ovary syndrome;    REV-ERBs;    mitochondrial biosynthesis;    autophagy;    follicular development;   

DOI  :  10.3389/fcell.2021.658112

来源: DOAJ

【 摘 要 】

Polycystic ovary syndrome (PCOS) is an endocrinopathy with complex pathophysiology that is a common cause of anovulatory infertility in women. Although the disruption of circadian rhythms is indicated in PCOS, the role of the clock in the etiology of these pathologies has yet to be appreciated. The nuclear receptors REV-ERBα and REV-ERBβ are core modulators of the circadian clock and participate in the regulation of a diverse set of biological functions. However, in PCOS, the expression of REV-ERBs and their effects remain unclear. Here, we demonstrate that the levels of REV-ERBα and REV-ERBβ expression were lower in the granulosa cells of PCOS patients than in control subjects. In vitro, we found that the overexpression of REV-ERBα and REV-ERBβ, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1α, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERBα and REV-ERBβ can inhibit apoptosis in granulosa cells and promote proliferation. Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.

【 授权许可】

Unknown