Exposure to DE-71 alters thyroid hormone levels and gene transcription in the hypothalamic-pituitary-thyroid axis of zebrafish larvae.
ABSTRACT Polybrominated diphenyl ethers (PBDEs) have the potential to disrupt thyroid hormone homeostasis, but the molecular mechanisms underlying this process have not yet been clarified. In the present study, zebrafish (Danio rerio) embryos were exposed to a low concentration (0, 1, 3, and 10microg/L) of DE-71 from fertilization to 14 days thereafter. The whole-body content of thyroid hormone and transcription of genes in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. Exposure to up to 10microg/L of DE-71 significantly reduced thyroxine (T4) levels and significantly upregulated the transcription of corticotrophin-releasing hormone (CRH) and thyroid-stimulating hormone (TSHbeta) genes in a concentration-dependent manner. The transcription of genes involved in the synthesis of TH proteins, sodium/iodide symporter (Slc5a5), and thyroglobulin (TG) and the transcription of marker genes associated with early thyroid development (Pax8 and Nkx2.1) were significantly upregulated upon DE-71 exposure. The expression of thyronine deiodinase (Deio1 and Deio2) mRNAs was also significantly upregulated, possibly as a compensatory response to the decreased T4 levels. However, DE-71 exposure resulted in the downregulation of transthyretin (TTR) gene transcription and did not affect the transcription of thyroid hormone receptors (TRs). Exposure to DE-71 significantly induced the transcription of the uridinediphosphate-glucuronosyltransferase (UGT1ab) gene. The results of our study confirmed the reliability of the zebrafish larvae as models for assessment of the developmental toxicity of PBDEs and transcription of genes of the HPT axis can evaluate the potential mechanisms of thyroid disruption.
Article: Accumulation and biotransformation of BDE-47 by zebrafish larvae and teratogenicity and expression of genes along the hypothalamus-pituitary-thyroid axis.[show abstract] [hide abstract]
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 hours post fertilization (hpf) to 120 hpf were investigated. The 96 h-LC50 of the most toxic compound, based on teratogenicity was 330 µg 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 6-OH-BDE-47/L or 5 mg 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. 6-OH-BDE-47. 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 appears to have less toxicological relevance than the two natural product analogues 6-OH- and 6-MeO-BDE-47.Environmental Science & Technology 10/2012; · 4.80 Impact Factor