Trichloroethylene (TCE), a widely used organic solvent, is a common environmental pollutant. Increasing evidence indicates that maternal TCE exposure is associated with congenital cardiac defects, but the underlining mechanisms remain largely unknown. In this study, we revealed that TCE exposure significantly induced heart defects and dysfunctions in zebrafish embryos. Heart tissues were dissected and subjected to high throughput sequencing and qPCR to identify differentially expressed miRNAs and mRNAs. The effects of miRNA were further verified by microinjection of antagomir or agomir. Reactive Oxygen Species (ROS) and cell proliferation were measured by using dichlorodihydrofluorescein diacetate (DCFH-DA) and EdU staining, respectively. Our results showed that 19 miRNAs were downregulated whereas 48 miRNAs were upregulated in the heart of zebrafish embryos. The downregulation of miR-133a and the upregulation of miR-182 were further validated. Moreover, we found that miR-133a agomir significantly alleviated the TCE-induced heart defects while miR-133a antagomir mimicked the toxic effect of TCE on heart development. Furthermore, miR-133a agomir significantly counteracted TCE-induced ROS production and excessive cell proliferation in the heart of zebrafish embryos. In conclusion, our results indicate that miR-133a mediates TCE-induced ROS generation, leading to excessive cell proliferation and heart defects.

中文翻译：

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miR-133a的下调有助于斑马鱼中三氯乙烯的心脏发育毒性。

三氯乙烯（TCE）是一种广泛使用的有机溶剂，是一种常见的环境污染物。越来越多的证据表明，孕妇TCE暴露与先天性心脏缺陷有关，但其下划线机制仍不清楚。在这项研究中，我们发现，TCE暴露会明显引起斑马鱼胚胎中的心脏缺陷和功能障碍。解剖心脏组织，并进行高通量测序和qPCR，以鉴定差异表达的miRNA和mRNA。通过微注射antagomir或agomir可进一步验证miRNA的作用。分别通过使用二乙酸二氯二氢荧光素（DCFH-DA）和EdU染色来测量活性氧（ROS）和细胞增殖。我们的结果表明，在斑马鱼胚胎的心脏中19个miRNA被下调，而48个miRNA被上调。进一步验证了miR-133a的下调和miR-182的上调。此外，我们发现miR-133a agomir显着减轻了TCE诱导的心脏缺陷，而miR-133a antagomir模仿了TCE对心脏发育的毒性作用。此外，miR-133a agomir显着抵消了斑马鱼胚胎心脏中TCE诱导的ROS产生和过度的细胞增殖。总之，我们的结果表明miR-133a介导TCE诱导的ROS生成，从而导致过度的细胞增殖和心脏缺陷。我们发现miR-133a agomir显着减轻了TCE诱发的心脏缺陷，而miR-133a antagomir模仿了TCE对心脏发育的毒性作用。此外，miR-133a agomir显着抵消了斑马鱼胚胎心脏中TCE诱导的ROS产生和过度的细胞增殖。总之，我们的结果表明miR-133a介导TCE诱导的ROS生成，从而导致过度的细胞增殖和心脏缺陷。我们发现miR-133a agomir显着减轻了TCE诱发的心脏缺陷，而miR-133a antagomir模仿了TCE对心脏发育的毒性作用。此外，miR-133a agomir可显着抵消斑马鱼胚胎心脏中TCE诱导的ROS产生和过度的细胞增殖。总之，我们的结果表明miR-133a介导TCE诱导的ROS生成，从而导致过度的细胞增殖和心脏缺陷。