Parental exposure to environmental concentrations of tris(1,3-dichloro-2-propyl)phosphate induces abnormal DNA methylation and behavioral changes in F1 zebrafish larvae

文献类型： 外文期刊

第一作者： Ding, Xisheng

作者： Ding, Xisheng;Sun, Wen;Liu, Chunsheng;Sun, Qian;Wang, Jianghua;Yu, Liqin;Dai, Lili;Liu, Chunsheng;Sun, Qian;Wang, Jianghua;Yu, Liqin;Zhang, Panwei;Li, Kun

作者机构：

关键词： TDCIPP; Parental exposure; DNA methylation; Neurotoxicity; Zebrafish

期刊名称：ENVIRONMENTAL POLLUTION （ 影响因子：8.071； 五年影响因子：8.35 ）

ISSN： 0269-7491

年卷期： 2020 年 267 卷

页码：

收录情况： SCI

摘要： Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been demonstrated to be transferred from parental animals to their offspring. However, whether parental exposure to environmental concentrations of TDCIPP show neurodevelopmental toxicity in the F1 generation and the possible underlying mechanism remain unclear. Therefore, in this study, zebrafish embryos were exposed to environmental concentrations of TDCIPP (3, 30 and 300 ng L-1) for 120 days. The effects of exposure on motor behaviors, neurotransmitter levels, DNA methylation, and gene expression of F1 larvae were investigated. Parental exposure left TDCIPP residues in F1 eggs as well as reduced body length of F1 larvae. Moreover, parental exposure significantly reduced swimming activity in F1 5 dpf larvae, although it did not significantly alter serotonin, dopamine, 3,4-dihydroxyphenylacetic acid, g-aminobutyrate, and acetylcholine levels. Genes encoding DNA methylation transferases (dnmt3aa and dnmt1) were downregulated in F1 larvae. Reduced representation bisulfite sequencing analysis revealed 446 differentially methylated regions and enriched neuronal cell body Gene Ontology term in F1 generation. Correlation analysis between the expression of genes related to neural cell body and swimming speed indicated that solute carrier family 1 member 2b (slc1a2b) downregulation might be responsible for the inhibition of motor behaviors. Furthermore, bisulfite amplicon sequencing analysis confirmed hypermethylation of the promoter region of slc1a2b in F1 larvae following parental exposure to 300 ng L-1 TDCIPP, which might have led to significant downregulation of gene expression and, in turn, influenced the motor behaviors. These results indicate that parental exposure to environmental concentrations of TDCIPP alters DNA methylation, down regulates gene expressions and, thus inducing developmental neurotoxicity, in F1 larvae. (c) 2020 Elsevier Ltd. All rights reserved.

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