Developmental toxicity of bromoacetamide via the thyroid hormone receptors-mediated disruption of thyroid hormone homeostasis in zebrafish embryos.

Bromoacetamide (BAcAm) is a nitrogenous disinfection by-product. We previously found that BAcAm induced developmental toxicity in zebrafish embryos, but the underlying mechanisms remain to be elucidated. Since thyroid hormones (THs) homeostasis is crucial to development, we hypothesized that disruption of THs homeostasis may play a role in the developmental toxicity of BAcAm. In this study, we found BAcAm exposure significantly increased mortality and malformation rate, decreased hatching rate and body length, inhibited the locomotor capacity in zebrafish embryos. BAcAm elevated TSH, T3 and T4 levels, down-regulated T3/T4 ratios, and up-regulated mRNA expression changes of THs related genes (trh, tsh, tg, nis, tpo, dio1, dio2, ugt1ab，klf9 and rho), but down-regulated mRNA expression changes of TH receptors (tr α and tr β). Up-regulated tr α and tr β mRNAs by rescue treatment confirmed that both tr α and tr β were involved in the developmental toxicity of BAcAm. In conclusion, our study indicates disruption of THs homeostasis via the thyroid hormone receptors was responsible for the developmental toxicity of BAcAm.