title: Estrogen receptor beta mediates hepatotoxicity induced by perfluorooctane sulfonate in mouse.
abstract: Perfluorooctane sulfonate (PFOS), an artificial fluorosurfactant and global contaminant, is used widely in various consumer products. In this study, we investigated the function of estrogen receptor β (ERβ) in PFOS-induced bile acid and cholesterol metabolism disorders and gut microbiome using ERβ knockout mice that were exposed to PFOS by gavage. Our results showed that a daily dose of 5 mg PFOS/kg significantly induced hydropic degeneration and vacuolation in hepatic cells, reduced bile acid, and cholesterol levels in liver tissue, and influenced the abundance and composition of gut microbiota. Notably, ERβ deficiency not only ameliorated morphological alterations of hepatocytes but also relieved disorders in bile acids and cholesterol metabolism caused by PFOS. Furthermore, the changes in the gut microbiome by PFOS were also modulated. The relative transcript abundance of key genes involved in bile acid and cholesterol metabolism exhibited similar changes. In HepG2 cells, PFOS increased ERβ expression, which could be blocked by adding PHTPP (a selective antagonist of ERβ). Our study thus provides new evidence that ERβ mediates PFOS-induced hepatotoxicity.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhao-Yan
authors.initials: ZY
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China. aihuagu@njmu.edu.cn.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. aihuagu@njmu.edu.cn.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005466:Fluorocarbons / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D051379:Mice
chemical_list: D017738:Alkanesulfonic Acids; D047629:Estrogen Receptor beta; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid
keywords: Estrogen receptor β; Gut microbiota; Hepatotoxicity; Perfluorooctane sulfonate