title: Metabolomics approach reveals metabolic disorders and potential biomarkers associated with the developmental toxicity of tetrabromobisphenol A and tetrachlorobisphenol A.
abstract: Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA. Unexpectedly, we observed enhanced neural activity accompanied by lactate accumulation and accelerated heart rates due to an increase in dopamine pathway and a decrease in inhibitory neurotransmitters following H-BPA exposure. Notably, disorders of the neural system, and disruptions in glycolysis, the TCA cycle, nucleoside metabolism, lipid metabolism, glutamate and aspartate metabolism induced by H-BPA exposure were heritable. Furthermore, lactate and dopa were identified as potential biomarkers of the developmental toxicity of H-BPA and related genetic effects. This study has demonstrated that the metabolomics approach is a useful tool for obtaining comprehensive and novel insights into the molecular developmental toxicity of environmental pollutants.
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Guozhu
authors.initials: G
authors.lastname: Ye
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hong-Ou
authors.initials: HO
authors.lastname: Wang
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Qiansheng
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Yulang
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Dong
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002733:Chlorophenols / Q000633:toxicity*; D002952:Citric Acid Cycle; D004305:Dose-Response Relationship, Drug; D006019:Glycolysis; D050356:Lipid Metabolism; D008659:Metabolic Diseases / Q000378:metabolism*; D055432:Metabolomics; D009705:Nucleosides / Q000378:metabolism; D009990:Oryzias / Q000196:embryology; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D002733:Chlorophenols; D009705:Nucleosides; D011075:Polybrominated Biphenyls; D013723:Teratogens; C041181:tetrachlorodian; C020806:tetrabromobisphenol A