State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Aquat Toxicol. 2010 May 5;97(3):226-33. doi: 10.1016/j.aquatox.2009.10.022. Epub 2009 Oct 30.
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.
多溴联苯醚（PBDEs）有可能破坏甲状腺激素的内稳态，但这一过程的分子机制尚未阐明。本研究采用斑马鱼（Danio rerio）胚胎模型，从受精开始至 14 天，分别暴露于低浓度（0、1、3 和 10μg/L）的 DE-71 中。分析了甲状腺激素的全身含量以及下丘脑-垂体-甲状腺（HPT）轴中基因的转录情况。暴露于高达 10μg/L 的 DE-71 可显著降低甲状腺素（T4）水平，并呈浓度依赖性显著上调促肾上腺皮质激素释放激素（CRH）和促甲状腺激素（TSHβ）基因的转录。TH 蛋白合成相关基因（钠/碘转运体（Slc5a5）和甲状腺球蛋白（TG））、早期甲状腺发育相关标记基因（Pax8 和 Nkx2.1）的转录均显著上调。甲状腺素脱碘酶（Deio1 和 Deio2）mRNA 的表达也显著上调，可能是对 T4 水平降低的代偿反应。然而，DE-71 暴露导致转甲状腺素（TTR）基因转录下调，而不影响甲状腺激素受体（TRs）的转录。DE-71 暴露显著诱导尿苷二磷酸-葡萄糖醛酸转移酶（UGT1ab）基因转录。本研究结果证实了斑马鱼幼虫作为评估 PBDEs 发育毒性的模型的可靠性，HPT 轴基因的转录可以评估甲状腺破坏的潜在机制。
