Exposure to DE-71 alters thyroid hormone levels and gene transcription in the hypothalamic-pituitary-thyroid axis of zebrafish larvae.
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.
Yu
Liqin
L
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Deng
Jun
J
Shi
Xiongjie
X
Liu
Chunsheng
C
Yu
Ke
K
Zhou
Bingsheng
B
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007814:Larva; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D012333:RNA, Messenger; D013963:Thyroid Hormones; D029961:Zebrafish Proteins; C086401:pentabromodiphenyl ether