Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signalling
Tetramethyl bisphenol F (TMBPF), regarded as a promising alternative to bisphenol A (BPA) across multiple industries, is now incorporated into polymer coatings for metal cans used in food and beverage packaging. Recent research has highlighted possible health risks associated with TMBPF, yet its imp...
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Elsevier
2025-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325002763 |
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| author | Huiyu Fan Chunming Li Yifei Lv Tongyun Qi Yizhou Huang Linjuan Ma Yibing Lan Peiqiong Chen Zheng Lou Jianhong Zhou |
| author_facet | Huiyu Fan Chunming Li Yifei Lv Tongyun Qi Yizhou Huang Linjuan Ma Yibing Lan Peiqiong Chen Zheng Lou Jianhong Zhou |
| author_sort | Huiyu Fan |
| collection | DOAJ |
| description | Tetramethyl bisphenol F (TMBPF), regarded as a promising alternative to bisphenol A (BPA) across multiple industries, is now incorporated into polymer coatings for metal cans used in food and beverage packaging. Recent research has highlighted possible health risks associated with TMBPF, yet its impact on ovarian function and the mechanisms involved remain inadequately understood. This study provides a thorough evaluation of TMBPF's effects on granulosa cells (GCs) and uncovers its transgenerational influence on female reproductive health. We exposed pregnant CD1 mice to TMBPF at doses of 50 μg/kg/day or 200 μg/kg/day from gestational day 7 (GD7) through postnatal day 21 (PND21). Our findings indicated that maternal exposure to TMBPF adversely affects the reproductive system of the F1 generation by elevating the levels of E2, FSH, and LH, reducing the ovarian index, and increasing the number of collagen fibers in the ovarian stroma. The human granulosa-like tumor cell line KGN was employed as an experimental model to assess the toxic effects of TMBPF on GCs. The findings revealed that sublethal concentrations of TMBPF induced mitochondrial dysfunction, cellular senescence, and disrupted redox homeostasis in GCs in vitro. Our transcriptome sequencing analyses indicated that ESRRB upregulation might play a critical role in TMBPF-induced cellular senescence. Additionally, TMBPF exposure induced KGN cells senescence and senescent cell accumulation in F1 mouse ovaries by promoting ESRRB/p21 signalling. Collectively, our results indicate that TMBPF disrupts hormone levels in the ovaries, accelerates GCs senescence and promotes ovarian fibrosis, adversely affecting ovarian function in offspring. This study provides new insights into the potential effects of TMBPF exposure on the reproductive system and the related mechanisms. |
| format | Article |
| id | doaj-art-8f0ae50583a94de49b1afd51622a6b45 |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-8f0ae50583a94de49b1afd51622a6b452025-08-20T02:06:19ZengElsevierEcotoxicology and Environmental Safety0147-65132025-03-0129211794010.1016/j.ecoenv.2025.117940Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signallingHuiyu Fan0Chunming Li1Yifei Lv2Tongyun Qi3Yizhou Huang4Linjuan Ma5Yibing Lan6Peiqiong Chen7Zheng Lou8Jianhong Zhou9Department of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Key Laboratory of Women’s Reproductive Health of Zhejiang Province, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Key Laboratory of Women’s Reproductive Health of Zhejiang Province, Hangzhou, PR China; Department of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Key Laboratory of Women’s Reproductive Health of Zhejiang Province, Hangzhou, PR China; Department of Gynecology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Key Laboratory of Women’s Reproductive Health of Zhejiang Province, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR ChinaDepartment of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, PR China; Correspondence to: Department of Gynecology, Women’s Hospital, Zhejiang University School of Medicine, 1 Xueshi Rd, Hangzhou 310006, PR China.Tetramethyl bisphenol F (TMBPF), regarded as a promising alternative to bisphenol A (BPA) across multiple industries, is now incorporated into polymer coatings for metal cans used in food and beverage packaging. Recent research has highlighted possible health risks associated with TMBPF, yet its impact on ovarian function and the mechanisms involved remain inadequately understood. This study provides a thorough evaluation of TMBPF's effects on granulosa cells (GCs) and uncovers its transgenerational influence on female reproductive health. We exposed pregnant CD1 mice to TMBPF at doses of 50 μg/kg/day or 200 μg/kg/day from gestational day 7 (GD7) through postnatal day 21 (PND21). Our findings indicated that maternal exposure to TMBPF adversely affects the reproductive system of the F1 generation by elevating the levels of E2, FSH, and LH, reducing the ovarian index, and increasing the number of collagen fibers in the ovarian stroma. The human granulosa-like tumor cell line KGN was employed as an experimental model to assess the toxic effects of TMBPF on GCs. The findings revealed that sublethal concentrations of TMBPF induced mitochondrial dysfunction, cellular senescence, and disrupted redox homeostasis in GCs in vitro. Our transcriptome sequencing analyses indicated that ESRRB upregulation might play a critical role in TMBPF-induced cellular senescence. Additionally, TMBPF exposure induced KGN cells senescence and senescent cell accumulation in F1 mouse ovaries by promoting ESRRB/p21 signalling. Collectively, our results indicate that TMBPF disrupts hormone levels in the ovaries, accelerates GCs senescence and promotes ovarian fibrosis, adversely affecting ovarian function in offspring. This study provides new insights into the potential effects of TMBPF exposure on the reproductive system and the related mechanisms.http://www.sciencedirect.com/science/article/pii/S0147651325002763Maternal exposureTMBPFCellular senescenceESRRBEndocrine-disrupting chemicals |
| spellingShingle | Huiyu Fan Chunming Li Yifei Lv Tongyun Qi Yizhou Huang Linjuan Ma Yibing Lan Peiqiong Chen Zheng Lou Jianhong Zhou Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signalling Ecotoxicology and Environmental Safety Maternal exposure TMBPF Cellular senescence ESRRB Endocrine-disrupting chemicals |
| title | Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signalling |
| title_full | Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signalling |
| title_fullStr | Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signalling |
| title_full_unstemmed | Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signalling |
| title_short | Tetramethyl bisphenol F exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating ESRRB signalling |
| title_sort | tetramethyl bisphenol f exposure induces human ovarian granulosa cell senescence and mouse ovarian damage by regulating esrrb signalling |
| topic | Maternal exposure TMBPF Cellular senescence ESRRB Endocrine-disrupting chemicals |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325002763 |
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