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A multi-omics approach reveals molecular mechanisms by which phthalates induce cardiac defects in zebrafish (Danio rerio)

文献类型： 外文期刊

作者： Mu, Xiyan 1 ; Chen, Xiaofeng 2 ; Liu, Jia 1 ; Yuan, Lilai 1 ; Wang, Donghui 3 ; Qian, Le 2 ; Qian, Yu 1 ; Shen, Gongming; 1 ;

作者机构： 1.Chinese Acad Fishery Sci, Fishery Resource & Environm Res Ctr, Beijing, Peoples R China

2.China Agr Univ, Coll Sci, Beijing, Peoples R China

3.Peking Univ, Coll Life Sci, Beijing, Peoples R China

关键词： Phthalates; Zebrafish embryo; Developmental toxicity; Molecular mechanisms; Cardiac defect

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 265 卷

页码：

收录情况： SCI

摘要： The potential risks of phthalates affecting human and animal health as well as the environment are emerging as serious concerns worldwide. However, the mechanism by which phthalates induce developmental effects is under debate. Herein, we found that embryonic exposure of zebrafish to di-(2ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) increased the rate of heart defects including abnormal heart rate and pericardial edema. Changes in the transcriptional profile demonstrated that genes involved in the development of the heart, such as tbx5b, nppa, ctnt, my17, cmlc1, were significantly altered by DEHP and DBP at 50 mu g/L, which agreed with the abnormal cardiac outcomes. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) further showed that significant hypomethylation of nppa and ctnt was identified after DEHP and DBP exposure, which was consistent with the up-regulation of these genes. Notably, hypermethylation on the promoter region (<1 kb) of tbx5b was found after DEHP and DBP exposure, which might be responsible for its decrease in transcription. In conclusion, phthalates have the potential to induce cardiac birth defects, which might be associated with the transcriptional regulation of the involved developmental factors such as tbx5b. These findings would contribute to understand the molecular pathways that mediated the cardiac defects caused by phthalates. (C) 2020 Elsevier Ltd. All rights reserved.

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