期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.658112
关键词
polycystic ovary syndrome; REV-ERBs; mitochondrial biosynthesis; autophagy; follicular development
资金
- National Nature Science Foundation of China [81671520, 81630035]
- Shanghai Municipal Commission of Science and Technology [18411964000]
PCOS, a common cause of anovulatory infertility in women, is associated with disrupted circadian rhythms. In this study, lower expression levels of REV-ERB alpha and REV-ERB beta were found in granulosa cells of PCOS patients. Overexpression of REV-ERB alpha and REV-ERB beta, as well as their agonist SR9009, promoted mitochondrial biosynthesis and inhibited autophagy in KGN cells, suggesting a potential therapeutic role in treating PCOS.
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-ERB alpha and REV-ERB beta 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-ERB alpha and REV-ERB beta expression were lower in the granulosa cells of PCOS patients than in control subjects. In vitro, we found that the overexpression of REV-ERB alpha and REV-ERB beta, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1 alpha, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERB alpha and REV-ERB beta 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.
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