Letter Cite This: Environ. Sci. Technol. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/journal/estlcu
Antagonistic Estrogenic Effects Displayed by Bisphenol AF and Perfluorooctanoic Acid on Zebrafish (Danio rerio) at an Early Developmental Stage Pengyu Chen,† Qiang Wang,† Meng Chen,† Jing Yang,† Ruihan Wang,‡ Wenjue Zhong,*,† Lingyan Zhu,*,† and Lihua Yang§
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†
Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Key Laboratory of Pollution Processes and Environmental Criteria of Ministry of Education, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China ‡ College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China § State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China S Supporting Information *
ABSTRACT: Bisphenol AF (BPAF) and perfluorooctanoic acid (PFOA) may display combined estrogenic effects on aquatic organisms, because BPAF and PFOA are widely present in the aquatic environment and reported to have estrogenic effects on aquatic organisms. In this study, zebrafish embryos were exposed to BPAF, PFOA, and binary mixtures of both for 7 days using estradiol (E2) and vitellogenin (VTG) as biomarkers. The estrogen receptor α (erα) expression and VTG level increased upon single exposures to BPAF (0.0372 and 0.372 μM) and PFOA (1.21 and 12.1 μM). Although both of them stimulated the P450 aromatase level, they displayed opposite effects on sex hormone-binding globulin. As a result, BPAF stimulated the E2 level but PFOA depressed it, and an antagonist effect on the E2 level was observed in the binary mixtures. The significant correlation between VTG level and erα expression suggested erα played a vital role in VTG synthesis. BPAF and PFOA could compete for the key common residue, Arg362, in the binding pocket of ERα, inducing antagonistic effects on erα-driven transcriptions. Thus, BPAF and PFOA displayed an antagonistic estrogenic effect on zebrafish during an early development stage.
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may cause combined toxicities to aquatic organisms.12 There are few studies about the combined toxicity of BPA analogues and PFASs. Perfluorooctanesulfonate (PFOS) suppressed the endocrine potential of BPA in terms of vitellogenin (VTG) induction in F1 male zebrafish.13 For embryonic stem cells, BPA displayed different interactive effects with PFOS and PFOA.14 Therefore, it is necessary to investigate the combined estrogenic effect of PFOA and BPA analogues. Given BPAF and PFOA displayed estrogen-like effects in vivo15−17 through estrogen receptor (ER)-mediated pathways,16−18 they may elicit combined estrogenic effects. Molecular docking was used to screen bioaccumulation potentials of structurally diverse PFASs and PFAS−protein interactions19 and was applied to study the interactions of BPA analogues with the human G protein-coupled estrogen
INTRODUCTION Bisphenol AF (BPAF), one of the most frequently applied BPA substitutes,1 has become a ubiquitous pollutant in the environment because of its increased levels of production and usage. It was detected at concentrations from 3.87 × 10−7 to 3.00 × 10−5 μM in the surface water of several rivers in China,2 and the concentration was as high as 50.0 nM in river water near a manufacturing plant in Zhejiang, China.3 The lethality and developmental and estrogenic effects of BPAF on zebrafish were greater than those of BPA.4,5 Perfluorooctanoic acid (PFOA) is one of the most frequently detected poly- and perfluoroalkyl substances (PFASs) in surface water around the world with concentrations ranging from several to hundreds of nanograms per liter,6,7 and even micrograms per liter in the effluent of a wastewater treatment plant.8 PFOA could act as a weak xenoestrogen.9 PFOA and BPAF are likely to coexist in the same aquatic environment simultaneously. The concentrations of PFOA and BPAF in Taihu Lake, China, were 16.9−39.7 and 140 ng/L, respectively.10,11 Contaminants co-present in one water system © XXXX American Chemical Society
Received: Revised: Accepted: Published: A
October October October October
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2018 2018 2018 2018 DOI: 10.1021/acs.estlett.8b00559 Environ. Sci. Technol. Lett. XXXX, XXX, XXX−XXX
Letter
Environmental Science & Technology Letters
Figure 1. Predicted binding modes obtained from the docking simulation analysis of BPAF and PFOA for zebrafish estrogen receptor α (ERα), CYP19A1, and PPARγ ligand-binding domains (LBDs): (A) BPAF−ERα complex, (B) PFOA−ERα complex, (C) BPAF−CYP19A1 complex, (D) PFOA−CYP19A1 complex, (E) BPAF−PPARγ complex, and (F) PFOA−PPARγ complex. The hydrogen bond is shown as a green dashed line with the indicated bond length. The common interacting residues for both ligands are encircled.
receptor (GPER)20 and ERα,21 showing BPAF bound to GPER and ERα more tightly than BPA, indicative of estrogenic effects that were stronger than those of BPA. Here we report the individual and combined estrogenic effects of BPAF and PFOA on zebrafish at an early development stage, using estradiol (E2) and VTG as biomarkers.5,22,23A variety of toxicological end points related to estrogenic effects were assessed. Molecular docking and molecular dynamic (MD) simulations were performed to understand the mechanisms.
embryos were pooled together as one replicate. The exposures were performed semistatically with half of the exposure solution replaced daily and lasted for 7 days. Survival rates and hatchability were recorded daily. In all the exposure groups after 96 h, the survival and hatching rates were not affected (Figure S1), and teratogenic effects (cardiac edema) were observed in only the HB group with a malformation rate of
