Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol A
Accumulating evidence identifies bisphenol A (BPA) as an endocrine disruptor with demonstrated hepatotoxicity, driving the adoption of structural analogs like bisphenol B (BPB). Pregnancy constitutes a critical developmental window for endocrine disruptor-mediated hepatotoxicity in offspring. Howeve...
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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/S0147651325010474 |
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| author | Huifeng Yue Yangcheng Hu Xiaoyun Wu Yuchai Tian Xiaomin Liang Jiyue Zhang Bin Li Huizhen Zhu Xiaotong Ji |
| author_facet | Huifeng Yue Yangcheng Hu Xiaoyun Wu Yuchai Tian Xiaomin Liang Jiyue Zhang Bin Li Huizhen Zhu Xiaotong Ji |
| author_sort | Huifeng Yue |
| collection | DOAJ |
| description | Accumulating evidence identifies bisphenol A (BPA) as an endocrine disruptor with demonstrated hepatotoxicity, driving the adoption of structural analogs like bisphenol B (BPB). Pregnancy constitutes a critical developmental window for endocrine disruptor-mediated hepatotoxicity in offspring. However, systematic toxicity evidence about BPB exposure-induced transgenerational hepatotoxicity in offspring remains scarce, and the regulatory mechanisms need to be further explored. To elucidate the gene markers and signaling pathways involved in the developmental origins of liver dysfunction induced by direct/maternal BPB exposure. In this study, we systematically analyzed the mechanism of hepatotoxicity and transgenerational effects of BPB by animal models (BPB, direct exposure and maternal exposure, 300 μg/kg bw (body weight)/day). Biochemical indicators and histopathological changes were examined, and bioinformatics analysis was used to explain the relationship between BPB exposure and the liver injuries. The results showed that direct BPB exposure induced subclinical hepatotoxicity with significant cholesterol reduction, circadian rhythm disruption, and Tmem87b/Fkbp1a-mediated chemoresistance. Maternal BPB exposure caused offspring hepatomegaly, transaminase elevation, drove oxidative stress and lipid metabolism imbalance through the Ppard-Slc23a2 dysregulation. Bioinformatics validation in human hepatocellular carcinoma (HCC) confirmed prognostic significance of Tmem87b/Fkbp1a/Ppard/Slc23a2. The study confirmed that BPB induces hepatotoxicity through circadian disruption and oxidative stress pathways, establishing these genes as dual biomarkers for early detection and therapeutic response prediction. |
| format | Article |
| id | doaj-art-3ff86582823e4f2b902dbedfc5471a0e |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-3ff86582823e4f2b902dbedfc5471a0e2025-08-20T03:03:53ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211870210.1016/j.ecoenv.2025.118702Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol AHuifeng Yue0Yangcheng Hu1Xiaoyun Wu2Yuchai Tian3Xiaomin Liang4Jiyue Zhang5Bin Li6Huizhen Zhu7Xiaotong Ji8Shanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China; Shandong Key Laboratory of Environmental Processes and Health, School of Environmental Science and Engineering, Shandong University, Qingdao, Shandong 266237, China; Corresponding author at: Shanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China.Shanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, ChinaShanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, ChinaShanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, ChinaShanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, ChinaShanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, ChinaShanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, ChinaShanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, ChinaDepartment of Environmental Health, School of Public Health, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Center for Ecological Public Health Security of Yellow River Basin, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaAccumulating evidence identifies bisphenol A (BPA) as an endocrine disruptor with demonstrated hepatotoxicity, driving the adoption of structural analogs like bisphenol B (BPB). Pregnancy constitutes a critical developmental window for endocrine disruptor-mediated hepatotoxicity in offspring. However, systematic toxicity evidence about BPB exposure-induced transgenerational hepatotoxicity in offspring remains scarce, and the regulatory mechanisms need to be further explored. To elucidate the gene markers and signaling pathways involved in the developmental origins of liver dysfunction induced by direct/maternal BPB exposure. In this study, we systematically analyzed the mechanism of hepatotoxicity and transgenerational effects of BPB by animal models (BPB, direct exposure and maternal exposure, 300 μg/kg bw (body weight)/day). Biochemical indicators and histopathological changes were examined, and bioinformatics analysis was used to explain the relationship between BPB exposure and the liver injuries. The results showed that direct BPB exposure induced subclinical hepatotoxicity with significant cholesterol reduction, circadian rhythm disruption, and Tmem87b/Fkbp1a-mediated chemoresistance. Maternal BPB exposure caused offspring hepatomegaly, transaminase elevation, drove oxidative stress and lipid metabolism imbalance through the Ppard-Slc23a2 dysregulation. Bioinformatics validation in human hepatocellular carcinoma (HCC) confirmed prognostic significance of Tmem87b/Fkbp1a/Ppard/Slc23a2. The study confirmed that BPB induces hepatotoxicity through circadian disruption and oxidative stress pathways, establishing these genes as dual biomarkers for early detection and therapeutic response prediction.http://www.sciencedirect.com/science/article/pii/S0147651325010474Bisphenol BDirect exposureMaternal exposureHepatotoxicityRNA-seqTransgenerational toxicity |
| spellingShingle | Huifeng Yue Yangcheng Hu Xiaoyun Wu Yuchai Tian Xiaomin Liang Jiyue Zhang Bin Li Huizhen Zhu Xiaotong Ji Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol A Ecotoxicology and Environmental Safety Bisphenol B Direct exposure Maternal exposure Hepatotoxicity RNA-seq Transgenerational toxicity |
| title | Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol A |
| title_full | Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol A |
| title_fullStr | Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol A |
| title_full_unstemmed | Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol A |
| title_short | Transgenerational hepatotoxicity induced by bisphenol B as a substitute for bisphenol A |
| title_sort | transgenerational hepatotoxicity induced by bisphenol b as a substitute for bisphenol a |
| topic | Bisphenol B Direct exposure Maternal exposure Hepatotoxicity RNA-seq Transgenerational toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325010474 |
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