The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualization
Bisphenol A (BPA) exposure has been widely associated with adverse health outcomes, prompting the proliferation of ''BPA-free'' products. However, substitutes such as bisphenol S (BPS) are now equally prevalent and frequently detected at levels comparable to BPA. Our previous res...
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325010826 |
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| author | Shaoyuan Xu Zhaoping Tan Ruiqing Zhang Jiawei Kang Zhenzhen Zhang Qin Fu Yun Tao Yao Xiong Yuanzhen Zhang |
| author_facet | Shaoyuan Xu Zhaoping Tan Ruiqing Zhang Jiawei Kang Zhenzhen Zhang Qin Fu Yun Tao Yao Xiong Yuanzhen Zhang |
| author_sort | Shaoyuan Xu |
| collection | DOAJ |
| description | Bisphenol A (BPA) exposure has been widely associated with adverse health outcomes, prompting the proliferation of ''BPA-free'' products. However, substitutes such as bisphenol S (BPS) are now equally prevalent and frequently detected at levels comparable to BPA. Our previous research identified BPA as an endocrine disruptor impairing reproductive systems. This study investigates the underexplored effects of BPS on endometrial decidualization and its underlying mechanisms. Serum and urine samples from infertility patients undergoing assisted reproductive technologies (ART) were analyzed for BPS concentrations, revealing a significantly lower implantation rate in the high serum BPS group compared to the low BPS group (37.5 % vs. 58.1 %, P = 0.048). Urinary BPS levels were elevated in patients with recurrent implantation failure (RIF) relative to controls (0.24 vs. 0.15 ng/mL). In vitro, human endometrial stromal cells (HESCs) exposed to BPS (100 pM–1 µM) during hormonally induced decidualization exhibited suppressed proliferation and reduced decidualization markers (PRL and IGFBP1). BPS exposure triggered endoplasmic reticulum (ER) stress, evidenced by elevated levels of ER stress-related proteins (XBP1-s, ATF4, and IRE1α), ultrastructural ER abnormalities observed via transmission electron microscopy, and increased immunostaining of IRE1α and ATF4 in RIF endometrial tissues. ER stress inhibitors (TUDCA and MKC8866) mitigated these effects and restored decidualization markers. Our findings suggest that BPS contamination may contribute to implantation failure by disrupting HESC decidualization through ER stress activation. |
| format | Article |
| id | doaj-art-d10a7e96a0fa45e188c987cdd9d776c7 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-d10a7e96a0fa45e188c987cdd9d776c72025-08-20T03:05:34ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211873710.1016/j.ecoenv.2025.118737The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualizationShaoyuan Xu0Zhaoping Tan1Ruiqing Zhang2Jiawei Kang3Zhenzhen Zhang4Qin Fu5Yun Tao6Yao Xiong7Yuanzhen Zhang8Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Reproductive Medicine Center, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China; Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan, Hubei 430071, China; Hubei Clinical Research Center for Reproductive Medicine, Shiyan, Hubei 442000, ChinaReproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan, Hubei 430071, ChinaReproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan, Hubei 430071, ChinaReproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan, Hubei 430071, ChinaReproductive Medicine Center, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China; Hubei Clinical Research Center for Reproductive Medicine, Shiyan, Hubei 442000, ChinaReproductive Medicine Center, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China; Hubei Clinical Research Center for Reproductive Medicine, Shiyan, Hubei 442000, ChinaReproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan, Hubei 430071, ChinaReproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan, Hubei 430071, China; Correspondence to: Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei 430071, China.Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan, Hubei 430071, China; Correspondence to: Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei 430071, China.Bisphenol A (BPA) exposure has been widely associated with adverse health outcomes, prompting the proliferation of ''BPA-free'' products. However, substitutes such as bisphenol S (BPS) are now equally prevalent and frequently detected at levels comparable to BPA. Our previous research identified BPA as an endocrine disruptor impairing reproductive systems. This study investigates the underexplored effects of BPS on endometrial decidualization and its underlying mechanisms. Serum and urine samples from infertility patients undergoing assisted reproductive technologies (ART) were analyzed for BPS concentrations, revealing a significantly lower implantation rate in the high serum BPS group compared to the low BPS group (37.5 % vs. 58.1 %, P = 0.048). Urinary BPS levels were elevated in patients with recurrent implantation failure (RIF) relative to controls (0.24 vs. 0.15 ng/mL). In vitro, human endometrial stromal cells (HESCs) exposed to BPS (100 pM–1 µM) during hormonally induced decidualization exhibited suppressed proliferation and reduced decidualization markers (PRL and IGFBP1). BPS exposure triggered endoplasmic reticulum (ER) stress, evidenced by elevated levels of ER stress-related proteins (XBP1-s, ATF4, and IRE1α), ultrastructural ER abnormalities observed via transmission electron microscopy, and increased immunostaining of IRE1α and ATF4 in RIF endometrial tissues. ER stress inhibitors (TUDCA and MKC8866) mitigated these effects and restored decidualization markers. Our findings suggest that BPS contamination may contribute to implantation failure by disrupting HESC decidualization through ER stress activation.http://www.sciencedirect.com/science/article/pii/S0147651325010826Bisphenol SEndometrial receptivityDecidualizationReproductive toxicEndoplasmic reticulum stress |
| spellingShingle | Shaoyuan Xu Zhaoping Tan Ruiqing Zhang Jiawei Kang Zhenzhen Zhang Qin Fu Yun Tao Yao Xiong Yuanzhen Zhang The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualization Ecotoxicology and Environmental Safety Bisphenol S Endometrial receptivity Decidualization Reproductive toxic Endoplasmic reticulum stress |
| title | The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualization |
| title_full | The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualization |
| title_fullStr | The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualization |
| title_full_unstemmed | The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualization |
| title_short | The role of endoplasmic reticulum stress in BPS-induced disruption of endometrial decidualization |
| title_sort | role of endoplasmic reticulum stress in bps induced disruption of endometrial decidualization |
| topic | Bisphenol S Endometrial receptivity Decidualization Reproductive toxic Endoplasmic reticulum stress |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325010826 |
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