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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-08-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.658112/full |
| _version_ | 1818599561263841280 |
|---|---|
| author | Lihua Sun Hui Tian Songguo Xue Hongjuan Ye Xue Xue Rongxiang Wang Yu Liu Caixia Zhang Qiuju Chen Shaorong Gao |
| author_facet | Lihua Sun Hui Tian Songguo Xue Hongjuan Ye Xue Xue Rongxiang Wang Yu Liu Caixia Zhang Qiuju Chen Shaorong Gao |
| author_sort | Lihua Sun |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-16T12:21:33Z |
| format | Article |
| id | doaj.art-aca8a87d7f824f55913b0c35dff5f2cc |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T12:21:33Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-aca8a87d7f824f55913b0c35dff5f2cc2022-12-21T22:31:57ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.658112658112Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary SyndromeLihua Sun0Hui Tian1Songguo Xue2Hongjuan Ye3Xue Xue4Rongxiang Wang5Yu Liu6Caixia Zhang7Qiuju Chen8Shaorong Gao9Department of Reproductive Medicine Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaDepartment of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Assisted Reproduction, Shanghai Ninth Peoples Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaInstitute 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, ChinaPolycystic 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.658112/fullpolycystic ovary syndromeREV-ERBsmitochondrial biosynthesisautophagyfollicular development |
| spellingShingle | Lihua Sun Hui Tian Songguo Xue Hongjuan Ye Xue Xue Rongxiang Wang Yu Liu Caixia Zhang Qiuju Chen Shaorong Gao 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 polycystic ovary syndrome REV-ERBs mitochondrial biosynthesis autophagy follicular development |
| 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 | polycystic ovary syndrome REV-ERBs mitochondrial biosynthesis autophagy follicular development |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.658112/full |
| work_keys_str_mv | AT lihuasun circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT huitian circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT songguoxue circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT hongjuanye circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT xuexue circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT rongxiangwang circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT yuliu circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT caixiazhang circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT qiujuchen circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome AT shaoronggao circadianclockgenesreverbsinhibitsgranulosacellsapoptosisbyregulatingmitochondrialbiogenesisandautophagyinpolycysticovarysyndrome |