Effects of perchlorate on BDE-47-induced alteration thyroid hormone and gene expression of in the hypothalamus–pituitary–thyroid axis in zebrafish larvae

• Co-exposure to BDE-47 and PER induced more developmental malformations compared to exposure to only BDE-47.
• Co-exposure resulted in lower T4 levels compared to exposure to only BDE-47.
• Co-exposure up-regulated the expression of the NIS, TG, Nkx2.1a genes and down-regulated the expression of the CRH and TSHβ genes compared to exposure to only BDE-47.
• Co-exposure up-regulated the expression of TG protein and down-regulated the expression of TTR protein compared to exposure to only BDE-47.

To investigate the effects of perchlorate on thyroid hormone disturbances induced by 2,2′,4′,4-tetrabromodiphenyl ether (BDE-47) via thyroid hormone (TH)-mediated pathways, zebrafish embryos were exposed to a combination of BDE-47 and PER from the time of fertilisation to 14 d (dpf). The whole-body content of TH and the expression of genes and proteins related to the hypothalamic–pituitary–thyroid (HPT) axis were analysed. Co-exposure to BDE-47 and PER decreased the body weight and increased malformation rates relative to the effects of exposure to only BDE-47. Compared with the exposure to BDE-47 alone, the exposure to a combination of BDE-47 (10 μg/L) and PER (3.5 mg/L) significantly up-regulated the expression of genes involved in TH synthesis (NIS and Nkx2.1a) and significantly down-regulated the expression of genes related to the regulation of the HPT axis (CRH and TSHβ). The expression of TG at the gene and protein levels was significantly up-regulated, but the expression of TTR was significantly down-regulated in the co-exposures relative to BDE-47 treated alone. In addition, the larger reduction in the T4 level resulting from exposure to the mixture of BDE-47 and PER demonstrated that PER enhanced the thyroid-disruptive effects of BDE-47. These results help to elucidate the complicated chemical interactions and the molecular mechanism of action of these two TH disruptors.