<i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway
Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by hyperandrogenemia with multiple suspended sinus follicles, thickened cortical tissue, and excessive proliferation of ovarian granulosa cells that severely affects the fertility and quality of life of women. The addition of &l...
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MDPI AG
2023-04-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/8/1927 |
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| author | Peiwen Zhang Yuheng Pan Shuang Wu Yuxu He Jinyong Wang Lei Chen Shunhua Zhang Hui Zhang Ye Zhao Lili Niu Mailin Gan Yan Wang Linyuan Shen Li Zhu |
| author_facet | Peiwen Zhang Yuheng Pan Shuang Wu Yuxu He Jinyong Wang Lei Chen Shunhua Zhang Hui Zhang Ye Zhao Lili Niu Mailin Gan Yan Wang Linyuan Shen Li Zhu |
| author_sort | Peiwen Zhang |
| collection | DOAJ |
| description | Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by hyperandrogenemia with multiple suspended sinus follicles, thickened cortical tissue, and excessive proliferation of ovarian granulosa cells that severely affects the fertility and quality of life of women. The addition of <i>n</i>-3 PUFA to the diet may slightly reduce body weight and greatly alleviate disturbed blood hormone levels in PCOS mice. We treated KGN as a cell model for <i>n</i>-3 PUFA addition and showed that <i>n</i>-3 PUFA inhibited the proliferation of GCs and promoted ferroptosis in ovarian granulosa cells. We used CCK-8, fluorescence quantitative transmission electron microscopy experiments and ferroptosis marker gene detection and other methods. Furthermore, <i>n</i>-3 PUFA was found to promote YAP1 exocytosis by activating Hippo and weakening the cross-talk between YAP1 and Nrf2 by activating the Hippo signaling pathway. In this study, we found that <i>n</i>-3 PUFA inhibited the over proliferation of granulosa cells in ovarian follicles by activating Hippo, promoting YAP1 exocytosis, weakening the cross-talk between YAP1 and Nrf2, and ultimately activating the ferroptosis sensitivity of ovarian granulosa cells. We demonstrate that <i>n</i>-3 PUFA can alleviate the hormonal and estrous cycle disorder with PCOS by inhibiting the YAP1-Nrf2 crosstalk that suppresses over proliferating ovarian granulosa cells and promotes iron death in GCs. These findings reveal the molecular mechanisms by which <i>n</i>-3 PUFA attenuates PCOS and identify YAP1-Nrf2 as a potential therapeutic target for regulation granulosa cells in PCOS. |
| first_indexed | 2024-03-11T04:40:04Z |
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| id | doaj.art-1ea6c1ae81d34145b59aeb96dbe5e212 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T04:40:04Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-1ea6c1ae81d34145b59aeb96dbe5e2122023-11-17T20:46:28ZengMDPI AGNutrients2072-66432023-04-01158192710.3390/nu15081927<i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo PathwayPeiwen Zhang0Yuheng Pan1Shuang Wu2Yuxu He3Jinyong Wang4Lei Chen5Shunhua Zhang6Hui Zhang7Ye Zhao8Lili Niu9Mailin Gan10Yan Wang11Linyuan Shen12Li Zhu13Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaChongqing Academy of Animal Science, Chongqing 402460, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaSichaun Center for Animal Disease Control, Chengdu 610041, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaPolycystic ovary syndrome (PCOS) is an endocrine disorder characterized by hyperandrogenemia with multiple suspended sinus follicles, thickened cortical tissue, and excessive proliferation of ovarian granulosa cells that severely affects the fertility and quality of life of women. The addition of <i>n</i>-3 PUFA to the diet may slightly reduce body weight and greatly alleviate disturbed blood hormone levels in PCOS mice. We treated KGN as a cell model for <i>n</i>-3 PUFA addition and showed that <i>n</i>-3 PUFA inhibited the proliferation of GCs and promoted ferroptosis in ovarian granulosa cells. We used CCK-8, fluorescence quantitative transmission electron microscopy experiments and ferroptosis marker gene detection and other methods. Furthermore, <i>n</i>-3 PUFA was found to promote YAP1 exocytosis by activating Hippo and weakening the cross-talk between YAP1 and Nrf2 by activating the Hippo signaling pathway. In this study, we found that <i>n</i>-3 PUFA inhibited the over proliferation of granulosa cells in ovarian follicles by activating Hippo, promoting YAP1 exocytosis, weakening the cross-talk between YAP1 and Nrf2, and ultimately activating the ferroptosis sensitivity of ovarian granulosa cells. We demonstrate that <i>n</i>-3 PUFA can alleviate the hormonal and estrous cycle disorder with PCOS by inhibiting the YAP1-Nrf2 crosstalk that suppresses over proliferating ovarian granulosa cells and promotes iron death in GCs. These findings reveal the molecular mechanisms by which <i>n</i>-3 PUFA attenuates PCOS and identify YAP1-Nrf2 as a potential therapeutic target for regulation granulosa cells in PCOS.https://www.mdpi.com/2072-6643/15/8/1927PCOSferroptosisYAP1<i>n</i>-3 PUFA |
| spellingShingle | Peiwen Zhang Yuheng Pan Shuang Wu Yuxu He Jinyong Wang Lei Chen Shunhua Zhang Hui Zhang Ye Zhao Lili Niu Mailin Gan Yan Wang Linyuan Shen Li Zhu <i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway Nutrients PCOS ferroptosis YAP1 <i>n</i>-3 PUFA |
| title | <i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway |
| title_full | <i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway |
| title_fullStr | <i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway |
| title_full_unstemmed | <i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway |
| title_short | <i>n</i>-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway |
| title_sort | i n i 3 pufa promotes ferroptosis in pcos gcs by inhibiting yap1 through activation of the hippo pathway |
| topic | PCOS ferroptosis YAP1 <i>n</i>-3 PUFA |
| url | https://www.mdpi.com/2072-6643/15/8/1927 |
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