Key result
Exposure of zebrafish embryos to TBOEP decreased body length, survival, hatching, and heart rates while increasing malformations, likely through down-regulation of the Wnt signaling pathway.
Why the study?
Although the developmental toxicity of tris (2-butoxyethyl) phosphate (TBOEP) in zebrafish larvae has been reported, few studies have focused on its underlying mechanisms.
TBOEP induces developmental and cardiotoxicity in zebrafish, mechanisms of which involve the down-regulation of the Wnt signaling pathway.
TBOEP may impair zebrafish development via identified pathways; hypothesis-generating for environmental risk and requires validation beyond animal models.
As a common organophosphorus flame retardant, tris (2-butoxyethyl) phosphate (TBOEP) is detected in water environment and aquatic animals extensively. Despite previous researches have reported the developmental toxicity of TBOEP in zebrafish (Danio rerio) larvae, few research focused on its underlying mechanisms. In this study, zebrafish embryos were exposed to 0, 20, 200, 1000 and 2000 µg/L TBOEP from 2 until 120 h post-fertilization (hpf) to determine potential mechanisms of developmental toxicity of this compound. Early developmental stage parameters such as body length, survival rate, hatching rate and heart rate were decreased, while malformation rate was ascended. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was carried out at 12, 24, 72 and 120 hpf to demonstrate alterations in expression of genes of Wnt signaling pathway. The results indicated that axin1 was significantly up-regulated, while β-catenin, pkc and wnt11 were down-regulated. Correlation analysis indicated that expression of these genes was significantly correlated with body length. Furthermore, apoptosis was detected in heart region by acridine orange (AO) staining and terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labeling (TUNEL) assay. In addition, at 120 hpf, occurrence of oxidative stress was observed in zebrafish larvae. Moreover, 6-Bromoindirubin-3'-oxime (BIO)， an activator of Wnt pathway, was found to alleviate the inhibiting effects of TBOEP on zebrafish growth. The overall outcomes offered novel viewpoints in toxic effects of TBOEP, and down-regulating Wnt signaling pathway were able to reveal some potential mechanisms of developmental toxicity of TBOEP in zebrafish larvae.
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Xiong et al. (2020) studied Developmental toxicity. Tris (2-butoxyethyl) phosphate (TBOEP) vs. 0 µg/L was evaluated on Early developmental stage parameters (body length, survival rate, hatching rate, heart rate, malformation rate) and Wnt signaling gene expression. Exposure of zebrafish embryos to TBOEP decreased body length, survival, hatching, and heart rates while increasing malformations, likely through down-regulation of the Wnt signaling pathway.
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