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Estrogen receptor beta mediates hepatotoxicity induced by perfluorooctane sulfonate in mouse

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81172694 and 81270537), the Outstanding Youth Fund of Jiangsu Province (SBK2014010296), the Research Project of Chinese Ministry of Education (213015A), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and Jiangsu Province’s QingLan project (JX2161015124).

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Author notes

  1. Cheng Xu, Zhao-Yan Jiang, and Qian Liu contributed equally to this study and should be regarded as joint first authors.

Authors and Affiliations

  1. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China

    Cheng Xu, Qian Liu, Hui Liu & Aihua Gu

  2. Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China

    Cheng Xu, Qian Liu, Hui Liu & Aihua Gu

  3. Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

    Zhao-Yan Jiang

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  1. Cheng Xu
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  2. Zhao-Yan Jiang
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  3. Qian Liu
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  4. Hui Liu
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  5. Aihua Gu
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Contributions

The authors’ contributions are as follows: Q.L. and C.X. conducted data analyses, and Z.Y.J. and A.H.G. were involved in the design of the study and interpretation of the results and critically reviewed the manuscript. All authors have approved the final manuscript.

Corresponding author

Correspondence to Aihua Gu.

Ethics declarations

All procedures performed in studies involving animals were in strict accordance with the ethical standards of the Animal Ethical Committee, Nanjing Medical University, China. This article does not contain any studies with human participants performed by any of the authors.

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The authors declare that they have no competing interests.

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Responsible editor: Philippe Garrigues

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Xu, C., Jiang, ZY., Liu, Q. et al. Estrogen receptor beta mediates hepatotoxicity induced by perfluorooctane sulfonate in mouse. Environ Sci Pollut Res 24, 13414–13423 (2017). https://doi.org/10.1007/s11356-017-8943-3

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