Department of Oriental Medicine Resources, Mokpo National University, Muan-gun, Jeonnam, 58554, Republic of Korea.
Department of Environmental Energy Engineering, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea.
Ecotoxicol Environ Saf. 2019 Oct 30;182:109449. doi: 10.1016/j.ecoenv.2019.109449. Epub 2019 Jul 27.
The flame retardant, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), is one of the most developmentally toxic organophosphate flame retardants (OPFRs). However, few mechanistic studies on phenotypic malformation caused by TDCIPP have been conducted. This study investigates the molecular mechanism underlying abnormal tail fin development consistently observed in zebrafish embryos exposed to TDCIPP. The results show that the defects in the tail fin (e.g., bent spine, defective caudal fin, and damaged tip) were associated with altered expression of transcription factors. The significant up-regulation of mmp9 and, among insulin-growth factor (IGF) families, igfbp-1a and igfbp1b was observed, whereas alterations in the expression of cdx4, igf1a, ifg1b, igf2b, and vegaa regulating tail development were dependent on time points. In accordance with changes in mRNA gene expression, TDCIPP impaired vessel formation and disorganized muscle in transgenic Tg(fli-GFP) zebrafish larvae. Furthermore, we found that the overexpression of mmp9 caused by TDCIPP was not linked to igfbp-1. Overall, these findings demonstrate that TDCIPP disrupts the progression of tail fin development, accompanied by defects in vessel and muscle formation in developing zebrafish embryos.
阻燃剂三(1,3-二氯-2-丙基)磷酸酯(TDCIPP)是最具发育毒性的有机磷酸酯阻燃剂(OPFRs)之一。然而,目前关于 TDCIPP 引起表型畸形的机制研究较少。本研究旨在探讨 TDCIPP 暴露的斑马鱼胚胎中一致观察到的异常尾鳍发育的分子机制。结果表明,尾鳍缺陷(如弯曲的脊柱、尾鳍缺陷和受损的尖端)与转录因子表达的改变有关。mmp9 的显著上调以及胰岛素样生长因子(IGF)家族中的 igfbp-1a 和 igfbp1b 被观察到,而调节尾发育的 cdx4、igf1a、ifg1b、igf2b 和 vegaa 的表达改变依赖于时间点。与 mRNA 基因表达的变化一致,TDCIPP 损害了转基因 Tg(fli-GFP)斑马鱼幼虫的血管形成和肌肉组织。此外,我们发现 TDCIPP 引起的 mmp9 过表达与 igfbp-1 无关。总的来说,这些发现表明 TDCIPP 破坏了尾鳍发育的进程,同时还导致了发育中的斑马鱼胚胎血管和肌肉形成的缺陷。