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Updated: Sep 18, 2025

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Estrogenic and transgenerational effects of perfluorocarboxylic acids through estrogen-related receptor γ pathway
Sha Shi1, Wei Zheng1, Xi-Long Zhang2
1College of Life Sciences, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China.
Abstract:
The estrogen-disrupting effects and mechanism of perfluorocarboxylic acids (PFCAs), with similar structures to perfluorooctanoic acid (PFOA), are poorly understood. The purpose of the present study is to explore the estrogen-disrupting effects of PFCAs through the estrogen-related receptor γ (ERRγ) pathway. In vitro, similar to an ERRγ agonist, perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), PFOA, perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) induced proliferation of human endometrial cancer cell Ishikawa at human exposure-related concentrations by binding and activating ERRγ. In vivo, PFHxA, PFOA and PFDA induced ovarian damage in zebrafish at 3.2 μM, 2.4 μM and 1.9 μM, respectively. PFCAs also induced sex hormones disturbance and interfered with sex hormone synthesis- and ERRγ pathway-related gene expression. In particular, PFOA exhibited estrogen-disturbing effects at the environmentally relevant concentration. Maternal exposure to PFCAs produced abnormal development of zebrafish offspring by disturbing the sex hormones and ERRγ pathway-related gene expression. All the effects were mitigated by an ERRγ antagonist. In conclusion, PFCAs could cause estrogen-disrupting effects and transgenerational effects through the ERRγ pathway. The study revealed a novel insight into the estrogen-disrupting effects of PFCAs.
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