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

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...

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Autores principales: Sun, Lihua, Tian, Hui, Xue, Songguo, Ye, Hongjuan, Xue, Xue, Wang, Rongxiang, Liu, Yu, Zhang, Caixia, Chen, Qiuju, Gao, Shaorong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374745/
https://www.ncbi.nlm.nih.gov/pubmed/34422794
http://dx.doi.org/10.3389/fcell.2021.658112
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author Sun, Lihua
Tian, Hui
Xue, Songguo
Ye, Hongjuan
Xue, Xue
Wang, Rongxiang
Liu, Yu
Zhang, Caixia
Chen, Qiuju
Gao, Shaorong
author_facet Sun, Lihua
Tian, Hui
Xue, Songguo
Ye, Hongjuan
Xue, Xue
Wang, Rongxiang
Liu, Yu
Zhang, Caixia
Chen, Qiuju
Gao, Shaorong
author_sort Sun, Lihua
collection PubMed
description 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.
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spelling pubmed-83747452021-08-20 Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome Sun, Lihua Tian, Hui Xue, Songguo Ye, Hongjuan Xue, Xue Wang, Rongxiang Liu, Yu Zhang, Caixia Chen, Qiuju Gao, Shaorong Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-08-05 /pmc/articles/PMC8374745/ /pubmed/34422794 http://dx.doi.org/10.3389/fcell.2021.658112 Text en Copyright © 2021 Sun, Tian, Xue, Ye, Xue, Wang, Liu, Zhang, Chen and Gao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sun, Lihua
Tian, Hui
Xue, Songguo
Ye, Hongjuan
Xue, Xue
Wang, Rongxiang
Liu, Yu
Zhang, Caixia
Chen, Qiuju
Gao, Shaorong
Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome
title Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome
title_full Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome
title_fullStr Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome
title_full_unstemmed Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome
title_short Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome
title_sort circadian clock genes rev-erbs inhibits granulosa cells apoptosis by regulating mitochondrial biogenesis and autophagy in polycystic ovary syndrome
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374745/
https://www.ncbi.nlm.nih.gov/pubmed/34422794
http://dx.doi.org/10.3389/fcell.2021.658112
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