Acute exposure to synthetic pyrethroids causes bioconcentration and disruption of the hypothalamus-pituitary-thyroid axis in zebrafish embryos

Synthetic pyrethroids (SPs) have the potential to disrupt the thyroid endocrine system in mammals; however, little is known of the effects of SPs and underlying mechanisms in fish. In the current study, embryonic zebrafish were exposed to various concentrations (1, 3 and 10 mu g/L) of bifenthrin (BF) or lambda-cyhalothrin (lambda-CH) until 72 h post fertilization, and body condition, bioaccumulation, thyroid hormone levels and transcription of related genes along the hypothalamus-pituitary-thyroid (HPT) axis examined. Bodyweightwas significantly decreased in the lambda-CH exposure groups, but not the BF exposure groups. BF and lambda-CH markedly accumulated in the larvae, with concentrations ranging from 90.7 to 596.8 ng/g. In both exposure groups, alterations were observed in thyroxine (T-4) and triiodothyronine (T-3) levels. In addition, the majority of the HPT axis-related genes examined, including CRH, TSH beta, TTR, UGT1ab, Pax8, Dio2 and TR alpha, were significantly upregulated in the presence of BF. Compared to BF, lambda-CH induced different transcriptional regulation patterns of the tested genes, in particular, significant stimulation of TTR, Pax8, Dio2 and TRa levels alongwith concomitant downregulation of Dio1. Molecular docking analyses revealed that at the atomic level, BF binds to thyroid hormone receptor (TR alpha) protein more potently than lambda-CH, consequently affecting HPT axis signal transduction. In vitro and in silico experiments disclosed that during the early stages of zebrafish development, BF and lambda-CH have the potential to disrupt thyroid endocrine system. (C) 2015 Elsevier B.V. All rights reserved.