Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathway
Objective The purpose of the study is to investigate therapeutic effects of metformin on improving PCOS and the underlying mechanism.Methods PCOS modeling and metformin treatment in rats was performed by subcutaneous injection of dehydroepiandrosterone (DHEA) daily, high-fat diet feeding, and intrag...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gynecological Endocrinology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/09513590.2025.2528815 |
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| author | Jin-Jing Li Hong-Lian Wu Yang Lv Ye-Min Qin Xi-Xi Qiu Xi-Xi Cai |
| author_facet | Jin-Jing Li Hong-Lian Wu Yang Lv Ye-Min Qin Xi-Xi Qiu Xi-Xi Cai |
| author_sort | Jin-Jing Li |
| collection | DOAJ |
| description | Objective The purpose of the study is to investigate therapeutic effects of metformin on improving PCOS and the underlying mechanism.Methods PCOS modeling and metformin treatment in rats was performed by subcutaneous injection of dehydroepiandrosterone (DHEA) daily, high-fat diet feeding, and intragastric administration of metformin for 21 consecutive days. PCOS modeling and metformin treatment in KGN cells was performed by DHEA treatment at a concentration of 10−5 mol/l for 48 h and metformin treatment (10−7 M) for 24 h.Results After PCOS modeling, rats showed more weight gain, improved glucose tolerance, disrupted estrous cycles, characteristic polycystic ovary morphology, more apoptotic cells in the ovary with enhanced oxidative stress, and declined Nrf2 and HO-1 expressions. Metformin treatment effectively alleviated characteristic polycystic ovary morphology, prevented apoptosis and oxidative stress, and decreased Nrf2 and HO-1 expressions of PCOS rats. Similarly, metformin treatment reduced the apoptosis and oxidative stress in DHEA-treated KGN cells, but anti-apoptotic and antioxidant effects of metformin were partially reversed by Nrf2 knockdown in DHEA-treated KGN cells.Conclusion The findings of the study suggest that metformin protects ovarian granulosa cells against oxidative stress and apoptosis in the context of PCOS via activation of Nrf2-HO-1 pathway. |
| format | Article |
| id | doaj-art-c21b8b080aad48c980e8fc9ed6f23b5e |
| institution | Matheson Library |
| issn | 0951-3590 1473-0766 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gynecological Endocrinology |
| spelling | doaj-art-c21b8b080aad48c980e8fc9ed6f23b5e2025-07-08T08:09:23ZengTaylor & Francis GroupGynecological Endocrinology0951-35901473-07662025-12-0141110.1080/09513590.2025.2528815Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathwayJin-Jing Li0Hong-Lian Wu1Yang Lv2Ye-Min Qin3Xi-Xi Qiu4Xi-Xi Cai5Center for Reproductive Medicine, Lishui People’s Hospital, Lishui, ChinaCenter for Reproductive Medicine, Lishui People’s Hospital, Lishui, ChinaCenter for Reproductive Medicine, Lishui People’s Hospital, Lishui, ChinaDepartment of Urology, Lishui People’s Hospital, Lishui, ChinaDepartment of Urology, Lishui People’s Hospital, Lishui, ChinaDepartment of Urology, Lishui People’s Hospital, Lishui, ChinaObjective The purpose of the study is to investigate therapeutic effects of metformin on improving PCOS and the underlying mechanism.Methods PCOS modeling and metformin treatment in rats was performed by subcutaneous injection of dehydroepiandrosterone (DHEA) daily, high-fat diet feeding, and intragastric administration of metformin for 21 consecutive days. PCOS modeling and metformin treatment in KGN cells was performed by DHEA treatment at a concentration of 10−5 mol/l for 48 h and metformin treatment (10−7 M) for 24 h.Results After PCOS modeling, rats showed more weight gain, improved glucose tolerance, disrupted estrous cycles, characteristic polycystic ovary morphology, more apoptotic cells in the ovary with enhanced oxidative stress, and declined Nrf2 and HO-1 expressions. Metformin treatment effectively alleviated characteristic polycystic ovary morphology, prevented apoptosis and oxidative stress, and decreased Nrf2 and HO-1 expressions of PCOS rats. Similarly, metformin treatment reduced the apoptosis and oxidative stress in DHEA-treated KGN cells, but anti-apoptotic and antioxidant effects of metformin were partially reversed by Nrf2 knockdown in DHEA-treated KGN cells.Conclusion The findings of the study suggest that metformin protects ovarian granulosa cells against oxidative stress and apoptosis in the context of PCOS via activation of Nrf2-HO-1 pathway.https://www.tandfonline.com/doi/10.1080/09513590.2025.2528815Polycystic ovary syndromemetformingranulosa cellsoxidative stressapoptosis |
| spellingShingle | Jin-Jing Li Hong-Lian Wu Yang Lv Ye-Min Qin Xi-Xi Qiu Xi-Xi Cai Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathway Gynecological Endocrinology Polycystic ovary syndrome metformin granulosa cells oxidative stress apoptosis |
| title | Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathway |
| title_full | Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathway |
| title_fullStr | Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathway |
| title_full_unstemmed | Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathway |
| title_short | Metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of Nrf2-HO-1 pathway |
| title_sort | metformin prevents oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome via activation of nrf2 ho 1 pathway |
| topic | Polycystic ovary syndrome metformin granulosa cells oxidative stress apoptosis |
| url | https://www.tandfonline.com/doi/10.1080/09513590.2025.2528815 |
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