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三(2-氯乙基)磷酸酯(TCEP)暴露抑制早期鸡胚的上皮-间充质转化(EMT)、中胚层分化和心血管发育。

Tris(2-chloroethyl) phosphate (TCEP) exposure inhibits the epithelial-mesenchymal transition (EMT), mesoderm differentiation, and cardiovascular development in early chicken embryos.

机构信息

Center for Marine Environmental Studies (CMES), Ehime University, 2-5 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan; National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan.

Center for Marine Environmental Studies (CMES), Ehime University, 2-5 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan.

出版信息

Sci Total Environ. 2024 Apr 20;922:171242. doi: 10.1016/j.scitotenv.2024.171242. Epub 2024 Feb 27.

Abstract

Tris(2-chloroethyl) phosphate (TCEP) is an organophosphorus flame retardant used worldwide and has been detected in the tissues and eggs of wild birds. Our previous study reported that exposure to TCEP induced developmental delay and cardiovascular dysfunction with attenuated heart rate and vasculogenesis in early chicken embryos. This study aimed to investigate the molecular mechanisms underlying the cardiovascular effects of TCEP on chicken embryos using cardiac transcriptome analysis and to examine whether TCEP exposure affects epithelial-mesenchymal transition (EMT) and mesoderm differentiation during gastrulation. Transcriptome analysis revealed that TCEP exposure decreased the expression of cardiac conduction-related genes and transcription factors on day 5 of incubation. In extraembryonic blood vessels, the expression levels of genes related to fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) were significantly reduced by TCEP exposure and vasculogenesis was suppressed. TCEP exposure also attenuated Snail family transcriptional repressor 2 (SNAI2) and T-box transcription factor T (TBXT) signaling in the chicken primitive streak, indicating that TCEP inhibits EMT and mesoderm differentiation during gastrulation at the early developmental stage. These effects on EMT and mesoderm differentiation may be related to subsequent phenotypic defects, including suppression of heart development and blood vessel formation.

摘要

三(2-氯乙基)磷酸酯(TCEP)是一种在世界范围内使用的有机磷阻燃剂,已在野生鸟类的组织和蛋中检测到。我们之前的研究报告称,TCEP 暴露会导致早期鸡胚发育迟缓、心血管功能障碍,心率减弱,血管生成减少。本研究旨在使用心脏转录组分析研究 TCEP 对鸡胚心血管作用的分子机制,并检查 TCEP 暴露是否会影响原肠胚形成期间的上皮-间充质转化(EMT)和中胚层分化。转录组分析显示,TCEP 暴露会降低孵化第 5 天心脏传导相关基因和转录因子的表达。在胚胎外血管中,TCEP 暴露会显著降低与成纤维细胞生长因子(FGF)和血管内皮生长因子(VEGF)相关的基因表达水平,并抑制血管生成。TCEP 暴露还减弱了鸡原肠胚中 Snail 家族转录抑制因子 2(SNAI2)和 T 盒转录因子 T(TBXT)信号,表明 TCEP 在早期发育阶段抑制 EMT 和中胚层分化。这些对 EMT 和中胚层分化的影响可能与随后的表型缺陷有关,包括心脏发育和血管形成的抑制。

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