title: Effects of perchlorate on BDE-47-induced alteration thyroid hormone and gene expression of in the hypothalamus-pituitary-thyroid axis in zebrafish larvae.
abstract: 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.
authors.affiliation: State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China; School of Municipal and Environmental Engineering, Harbin Institute of Technology, Harbin 150090, China. Electronic address: zhaoxuesong008@163.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Zhao
authors.forename: Shutao
authors.initials: S
authors.lastname: Wang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.forename: Xin
authors.initials: X
authors.lastname: Ren
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004784:Environmental Monitoring; D005411:Flame Retardants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007814:Larva; D010472:Perchlorates / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D013723:Teratogens; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000096:biosynthesis*; D013974:Thyroxine / Q000096:biosynthesis / Q000378:metabolism; D014284:Triiodothyronine / Q000096:biosynthesis / Q000378:metabolism; D015027:Zebrafish / Q000502:physiology*
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D010472:Perchlorates; D013723:Teratogens; D013963:Thyroid Hormones; D014284:Triiodothyronine; C511295:2,2',4,4'-tetrabromodiphenyl ether; D012313:RNA; D013974:Thyroxine
keywords: BDE-47; Gene expression; HPT axis; PER; Protein expression; Thyroid hormone