Perfluorobutanoic acid: A short-chain perfluoroalkyl substance exhibiting estrogenic effects through the estrogen-related receptor γ pathways

Fangfang Li; Lu Chen; Sha Shi; Wen-Jun Hong; Minjie Li; Liang-Hong Guo

doi:10.1016/j.jhazmat.2024.136947

Perfluorobutanoic acid: A short-chain perfluoroalkyl substance exhibiting estrogenic effects through the estrogen-related receptor γ pathways

J Hazard Mater. 2024 Dec 18:485:136947. doi: 10.1016/j.jhazmat.2024.136947. Online ahead of print.

Authors

Fangfang Li¹, Lu Chen², Sha Shi², Wen-Jun Hong¹, Minjie Li³, Liang-Hong Guo⁴

Affiliations

¹ College of Energy Environment and Safety Engineering, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China.
² Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China; College of Life Sciences, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China.
³ College of Energy Environment and Safety Engineering, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: mjli@cjlu.edu.cn.
⁴ College of Energy Environment and Safety Engineering, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: lhguo@cjlu.edu.cn.

PMID: 39708599
DOI: 10.1016/j.jhazmat.2024.136947

Abstract

Perfluorobutanoic acid (PFBA) is an emerging contaminant that was demonstrated to exhibit estrogen effects via action on classic estrogen receptors (ERs) in a low-activity manner. The purpose of the present study is to reveal the estrogen disruption effect and mechanism of PFBA via estrogen-related receptor γ (ERRγ) pathways. In vivo experiment indicated that PFBA accumulated in zebrafish ovary and caused ovarian injury, with disturbing sex hormone levels and interfering gene expression related to estrogen synthesis and follicle regulation. In vitro, with cell proliferation assay, PFBA could promote estrogen-sensitive endometrial cancer cell Ishikawa proliferation at lowest observed effective concentrations (LOEC) 10 nM, which was close to human exposure levels. And cell proliferation was inhibited by ERRγ antagonist GSK5182. By fluorescence competitive binding assay, molecular docking and luciferase reporter gene assays, it demonstrated that PFBA could directly bind with ERRγ and activate ERRγ transcriptional activities with a LOEC of 10 nM. Furthermore, PFBA up-regulated the proliferation-related factors downstream of ERRγ and inhibited by PI3K/Akt inhibitor LY294002, which also suppressed the cell proliferation induced by PFBA. Taken together, the results revealed that PFBA had estrogen effects at the human-related exposure concentration, and demonstrated a new estrogen effects mechanism of PFBA via ERRγ pathway.

Keywords: Estrogen effect; Estrogen-related receptor γ; Molecular mechanism; Perfluorobutanoic acid.