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依特硝唑暴露的斑马鱼胚胎转录组谱分析揭示了与心脏和眼部毒性相关的途径。

Transcriptome Profiling of Etridiazole-Exposed Zebrafish () Embryos Reveals Pathways Associated with Cardiac and Ocular Toxicities.

机构信息

Toxicity and Risk Assessment Division, Department of Agro-Food Safety and Crop Protection, National Institute of Agricultural Sciences, Rural Development Administration, Iseo-myeon, Wanju-gun 55365, Jeollabuk-do, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Oct 11;24(20):15067. doi: 10.3390/ijms242015067.

Abstract

Etridiazole (EDZ) is a thiadiazole-containing fungicide commonly used to control and spp. Although previous studies have shown that EDZ is teratogenic, the exact molecular mechanisms underlying its toxicity remain unknown. In this study, a zebrafish (; ZF) model was used to explore the molecular pathways associated with EDZ toxicity. The whole transcriptome of ZF embryos exposed to 96 h of EDZ was analyzed, along with developmental abnormalities. EDZ-induced malformations were primarily related to the eyes, heart, and growth of the ZF. Compared to untreated ZF, etridiazole-treated ZF had 2882 differentially expressed genes (DEGs), consisting of 1651 downregulated genes and 1231 upregulated genes. Gene ontology enrichment analysis showed that DEGs were involved in biological processes, such as sensory perception, visual perception, sensory organ development, and visual system development, and showed transmembrane transporter and peptidase regulator activities. Metabolism, phototransduction, aminoacyl-tRNA biosynthesis, MAPK signaling pathway, calcium signaling pathway, and vascular smooth muscle contraction were among the most enriched KEGG pathways. The qPCR analyses of the eight random genes were in good agreement with the transcriptome data. These results suggest several putative mechanisms underlying EDZ-induced developmental deformities in ZF.

摘要

噻二唑类杀菌剂乙嘧酚常用于防治和 spp。尽管先前的研究表明乙嘧酚具有致畸性,但它的毒性的确切分子机制仍不清楚。在这项研究中,使用斑马鱼(;ZF)模型来探索与乙嘧酚毒性相关的分子途径。分析了暴露于乙嘧酚 96 小时的 ZF 胚胎的全转录组,并观察了发育异常。乙嘧酚诱导的畸形主要与 ZF 的眼睛、心脏和生长有关。与未处理的 ZF 相比,乙嘧酚处理的 ZF 有 2882 个差异表达基因(DEGs),包括 1651 个下调基因和 1231 个上调基因。基因本体富集分析表明,DEGs 参与了生物过程,如感觉感知、视觉感知、感觉器官发育和视觉系统发育,以及表现出跨膜转运蛋白和肽酶调节剂的活性。代谢、光转导、氨酰-tRNA 生物合成、MAPK 信号通路、钙信号通路和血管平滑肌收缩是最富集的 KEGG 通路之一。对 8 个随机基因的 qPCR 分析与转录组数据吻合良好。这些结果表明了乙嘧酚在 ZF 中引起发育畸形的几种潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6740/10606920/1cd062da5cec/ijms-24-15067-g001.jpg

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