Metabolism disruption analysis of zebrafish larvae in response to BPA and BPA analogs based on RNA-Seq technique
Metabolism disruption analysis of zebrafish larvae in response to BPA and BPA analogs based on RNA-Seq technique
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基于 RNA-Seq 技术的斑马鱼幼虫对 BPA 和 BPA 类似物的代谢破坏分析
DOI：
10.1016/j.ecoenv.2019.01.126
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发表时间：
2019
影响因子：
6.8
通讯作者：
Zheng Chunmiao
中科院分区：
文献类型：
--
作者：
Qiu Wenhui;Liu Shuai;Liu Shuai;Yang Feng;Yang Feng;Dong Peiyao;Dong Peiyao;Yang Ming;Yang Ming;Wong Minghung;Wong Minghung;Zheng Chunmiao;Zheng Chunmiao
双酚A（BPA）是一种普遍存在于环境中的化学品，广泛用于工业中，已知对生物体有不利影响。鉴于其负面影响，已经开发了不含BPA的产品，其中含有BPA类似物，如双酚F（BPF）和双酚S（BPS）;然而，这些类似物被证明具有与BPA类似的毒性。在本研究中，我们的目的是通过对斑马鱼胚胎进行全局转录组测序（RNA-Seq），在转录水平上识别和比较BPA、BPF和BPS的潜在毒性机制。RNA-seq结果显示，100 μg/L BPA、BPF和BPS处理120 h后，斑马鱼胚胎中分别有285、191和246个基因的表达水平发生了显著变化。在表现出改变表达的基因中，有相当多的基因是两个或三个暴露组所共有的，这表明三种双酚之间的毒性一致。我们进一步通过qRT-PCR对19个差异表达基因的表达水平进行了验证，并对0.01、1和100 μg/L双酚处理后的RNA样品在相同条件下进行了测序，结果与RNA-Seq相似。此外，功能富集分析表明，代谢是双酚处理斑马鱼幼虫的主要干扰途径。蛋白质-蛋白质相互作用网络分析表明，在斑马鱼的药物代谢过程中，ces、cda、dpyd、upp 1、upp 2和cmpk 2等6个DEG相互作用。综上所述，我们的研究首次揭示了双酚处理后斑马鱼幼体基因转录的变化，表明BPF和BPS可能通过参与各种生物过程引起类似于BPA的不良反应，为进一步研究BPA类似物的毒理学提供了坚实的基础。
Bisphenol A (BPA) is an environmentally ubiquitous chemical widely used in industry and is known to have adverse effects on organisms. Given the negative effect, BPA-free products have been developed with BPA analogs such as bisphenol F (BPF) and bisphenol S (BPS); however, these analogs are proving to exhibit toxicity similar to that of BPA. In the present study, we aimed to identify and compare the underlying mechanisms of toxicity of BPA, BPF, and BPS at the transcriptional level by conducting global transcriptome sequencing (RNA-Seq) on zebrafish embryos. RNA-seq results showed that the expression levels of 285, 191, and 246 genes were significantly changed in zebrafish larvae after embryos were treated for 120 h with 100 μg/L BPA, BPF, and BPS, respectively. Among the genes exhibiting altered expression, a substantial number were common to two or three exposure groups, suggesting consistent toxicity between the three bisphenols. We further validated the expression levels of 19 differentially expressed genes by qRT-PCR, using sequencing RNA and the RNA samples after treatment by 0.01, 1, and 100 μg/L bisphenols under identical condition, the results were similar to RNA-Seq. Moreover, functional enrichment analysis indicated that metabolism was the main pathway which disrupted in zebrafish larvae by bisphenols treatment. Protein–protein interaction network analysis indicated that six DEGs (ces, cda, dpyd, upp1,upp2, and cmpk2) interact together in the drug metabolism of zebrafish. In summary, our study revealed changes in the transcription of genes upon bisphenols treatment in zebrafish larvae for the first time, indicating that BPF and BPS may cause adverse effects similar to BPA via their involvement in various biological processes, providing a solid foundation for further research on the toxicology of BPA analogs.