title: Endocrine-related effects of perfluorooctanoic acid (PFOA) in zebrafish, H295R steroidogenesis and receptor reporter gene assays.
abstract: Perfluorooctanoic acid (PFOA), a persistent perfluorinated compound, is distributed widely in wildlife and humans. Recent studies showed that PFOA is a suspected endocrine disruptor. But the results are somewhat contradictory and the mechanisms are unclear. In this study, we investigated the endocrine-related effects of PFOA using a series of assays. The lower dose effect of PFOA on development and endocrine-related gene expression were assessed in a short-term zebrafish assay in vivo. To clarify the mechanism of PFOA, in vitro assays were performed. We tested the hormone receptor activities of ER, AR, and TR against PFOA using reporter gene assays. The hormone levels of estradiol (E2) and testosterone (T), the expression of major steroidogenic genes and the key steroidogenic gene regulator steroidogenic factors 1 (SF-1) were measured after PFOA exposure in H295R steroidogenesis assay. Exposure of zebrafish embryo to PFOA resulted in higher expression of esr1, hhex and pax. PFOA is able to interfere with hormone receptor ER and TR. In H295R cells, PFOA could increase the E2 production and decrease the T production, altered the expression of major steroidogenic genes and regulator SF-1. The current findings indicated the potential endocrine-related effects of PFOA and provided novel information for human risk assessment.
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.
authors: Guizhen
authors: G
authors: Du
authors: Hongyu
authors: H
authors: Huang
authors: Jialei
authors: J
authors: Hu
authors: Yufeng
authors: Y
authors: Qin
authors: Di
authors: D
authors: Wu
authors: Ling
authors: L
authors: Song
authors: Yankai
authors: Y
authors: Xia
authors: Xinru
authors: X
authors: Wang
mesh_terms: D000818:Animals; D001681:Biological Assay; D002210:Caprylates / Q000633:toxicity*; D002460:Cell Line; D052244:Endocrine Disruptors / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D005466:Fluorocarbons / Q000633:toxicity*; D017930:Genes, Reporter; D013739:Testosterone / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D002210:Caprylates; D052244:Endocrine Disruptors; D005466:Fluorocarbons; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; D013739:Testosterone; D004958:Estradiol; C023036:perfluorooctanoic acid