Perinatal Bisphenol S Exposure Induces Hepatotoxicity in Female Rat Offspring: Insights into Disrupted Hepatic Cholesterol Homeostasis.
5 affiliations
- 1School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China.
- 2Department of Pediatrics, Institute of Pediatric Diseases and Rare Diseases, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China.
- 3Hubei Shizhen Laboratory, Wuhan 430061, China.
- 4The First Clinical Medical School, Hubei University of Chinese Medicine, Wuhan 430065, China.
- 5Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China.
Abstract
Recent research has highlighted concerns regarding the hepatotoxicity of Bisphenol S (BPS), particularly its potential transgenerational effects. In this study, we investigated the effects of perinatal BPS exposure on female offspring (F1) by exposing pregnant Sprague-Dawley (SD) rats (F0) to 0.05 and 20 mg/kg BPS from gestational day 6 to postnatal day 21. Results showed that perinatal BPS exposure resulted in increased body weight, higher liver coefficient, and impaired liver function in female rat offspring (F1). Untargeted metabolomics analysis revealed suppression of the primary bile acid biosynthesis pathway, and network toxicology predicted cholesterol metabolism and bile secretion as key pathways, suggesting altered cholesterol and bile acid homeostasis in the liver of female offspring. Validation studies demonstrated activation of cholesterol synthesis, as shown by upregulation of sterol regulatory element-binding protein 2 (SREBP2), squalene epoxidase (SQLE), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Furthermore, the down-regulated expression levels of acetyl-CoA acetyltransferase 1 (ACAT1), ATP-binding cassette sub-family G member 8 (ABCG8), and ATP-binding cassette sub-family G member 5 (ABCG5) indicated that pathways associated with cholesterol conversion, including cholesterol esterification, transport, and secretion as very low-density lipoprotein cholesterol (VLDL-C), were suppressed. Specifically, reduced transcription of ACAT1, ABCG8, and ABCG5, which are involved in cholesterol esterification and cholesterol efflux, was observed. This imbalance was associated with hepatic cholesterol accumulation and hepatotoxicity, although whether cholesterol accumulation was a cause or a consequence of liver injury remained unclear. In summary, our findings demonstrate that perinatal BPS exposure disrupted hepatic cholesterol homeostasis, which was associated with cholesterol accumulation and hepatotoxicity in F1 female rats.
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BibTeX
@article{huang2026perinatal,
title = {{Perinatal Bisphenol S Exposure Induces Hepatotoxicity in Female Rat Offspring: Insights into Disrupted Hepatic Cholesterol Homeostasis.}},
author = {Hongming Huang and Jingyi Zhang and Jing Jin and Ying Xie and Rui Pan and Min Zhao and Biran Zhu and Jianghuan Hua},
journal = {Toxics},
year = {2026},
month = sep,
doi = {10.3390/toxics14100878},
url = {https://europepmc.org/article/MED/42931665},
note = {CC BY},
}
RIS
TY - JOUR
TI - Perinatal Bisphenol S Exposure Induces Hepatotoxicity in Female Rat Offspring: Insights into Disrupted Hepatic Cholesterol Homeostasis.
AU - Hongming Huang
AU - Jingyi Zhang
AU - Jing Jin
AU - Ying Xie
AU - Rui Pan
AU - Min Zhao
AU - Biran Zhu
AU - Jianghuan Hua
PY - 2026
DA - 2026/09/30
JO - Toxics
DO - 10.3390/toxics14100878
UR - https://europepmc.org/article/MED/42931665
AB - Recent research has highlighted concerns regarding the hepatotoxicity of Bisphenol S (BPS), particularly its potential transgenerational effects. In this study, we investigated the effects of perinatal BPS exposure on female offspring (F1) by exposing pregnant Sprague-Dawley (SD) rats (F0) to 0.05 and 20 mg/kg BPS from gestational day 6 to postnatal day 21. Results showed that perinatal BPS exposure resulted in increased body weight, higher liver coefficient, and impaired liver function in female rat offspring (F1). Untargeted metabolomics analysis revealed suppression of the primary bile acid biosynthesis pathway, and network toxicology predicted cholesterol metabolism and bile secretion as key pathways, suggesting altered cholesterol and bile acid homeostasis in the liver of female offspring. Validation studies demonstrated activation of cholesterol synthesis, as shown by upregulation of sterol regulatory element-binding protein 2 (SREBP2), squalene epoxidase (SQLE), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Furthermore, the down-regulated expression levels of acetyl-CoA acetyltransferase 1 (ACAT1), ATP-binding cassette sub-family G member 8 (ABCG8), and ATP-binding cassette sub-family G member 5 (ABCG5) indicated that pathways associated with cholesterol conversion, including cholesterol esterification, transport, and secretion as very low-density lipoprotein cholesterol (VLDL-C), were suppressed. Specifically, reduced transcription of ACAT1, ABCG8, and ABCG5, which are involved in cholesterol esterification and cholesterol efflux, was observed. This imbalance was associated with hepatic cholesterol accumulation and hepatotoxicity, although whether cholesterol accumulation was a cause or a consequence of liver injury remained unclear. In summary, our findings demonstrate that perinatal BPS exposure disrupted hepatic cholesterol homeostasis, which was associated with cholesterol accumulation and hepatotoxicity in F1 female rats.
SN - 2305-6304
ER -