title: Accumulation and biotransformation of BDE-47 by zebrafish larvae and teratogenicity and expression of genes along the hypothalamus-pituitary-thyroid axis.
abstract: Accumulation and effects of BDE-47 and two analogues, 6-OH-BDE-47 and 6-MeO-BDE-47, on ontogeny and profiles of transcription of genes along the hypothalamus-pituitary-thyroid (HPT) axis of zebrafish (Danio rerio) embryos exposed from 4 h post fertilization (hpf) to 120 hpf were investigated. The 96 h-LC(50) of the most toxic compound, based on teratogenicity, was 330 μg of 6-OH-BDE-47/L. 6-OH-BDE-47 significantly down-regulated expression of mRNA of thyroid stimulating hormone receptor (TSHR), thyroid hormone receptors (TRs, including TRα and TRβ), sodium/iodide symporter (NIS), and transthyretin (TTR) while up-regulating expression of thyroglobulin (TG) and thyrotropin-releasing hormone (TRH). Spontaneous movement was affected by 1 mg of 6-OH-BDE-47/L or 5 mg of 6-MeO-BDE-47/L. BDE-47 did not alter activity of larvae at any concentration tested. 6-MeO-BDE-47 significantly up-regulated expression of mRNA of TRH, TRα, TRβ and NIS. Both 6-OH-BDE-47 and 6-MeO-BDE-47 affected the thyroid hormone pathway. BDE-47 and 6-MeO-BDE-47 were accumulated more than 6-OH-BDE-47. 6-MeO-BDE-47 was transformed into 6-OH-BDE-47, but BDE-47 was not transformed into it. In summary, the synthetic brominated flame retardant, BDE-47, did not elicit the adverse effects caused by the other two analogues and appeared to have less toxicological relevance than the two natural product analogues 6-OH- and 6-MeO-BDE-47.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Zheng
authors.forename: Yuting
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Liu
authors.forename: Hongling
authors.initials: H
authors.lastname: Liu
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
authors.forename: Michael H W
authors.initials: MH
authors.lastname: Lam
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; D014874:Water Pollutants, Chemical; C511295:2,2',4,4'-tetrabromodiphenyl ether