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Ecotoxicol Environ Saf. 2019 Oct 30;182:109449. doi: 10.1016/j.ecoenv.2019.109449. Epub 2019 Jul 27.

Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) disrupts zebrafish tail fin development.

Author information

1
Department of Oriental Medicine Resources, Mokpo National University, Muan-gun, Jeonnam, 58554, Republic of Korea.
2
Department of Environmental Energy Engineering, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea.
3
Department of Environment and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331, USA.
4
Department of Environmental Energy Engineering, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea; Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea. Electronic address: ktkim@seoultech.ac.kr.

Abstract

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.

KEYWORDS:

Developmental toxicity; OPFRs; TDCIPP; Tail malformation; Zebrafish

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