Biochemistry Program, School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Aquat Toxicol. 2012 Feb;108:106-11. doi: 10.1016/j.aquatox.2011.10.013. Epub 2011 Oct 28.
We performed waterborne exposures of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), tetrabromobisphenol A (TBBPA) or bisphenol A (BPA) on zebrafish (Danio rerio) embryo-larvae and quantitatively measured the expression of genes belonging to the hypothalamic-pituitary-thyroid (HPT) axis to assess for adverse thyroid function. For analysis on the effects of BDE-47, TBBPA and BPA on the hypothalamic-pituitary-thyroid genes, zebrafish embryo-larvae were acutely exposed to lethal concentrations of the chemical agents in order to determine the 96 h-LC50 (96 h lethal median concentration) and 96 h-EC50 (96 h effective median concentration) values. Further exposures at sub-lethal concentrations were then carried out and total RNA samples were extracted to quantify the mRNA expression levels of the genes of interest. In larvae, BDE-47 was found to have significantly induced many genes of interest, namely thyroglobulin, thyroid peroxidase, thyroid receptors α and β, thyroid stimulating hormone, and transthyretin. TBBPA only significantly induced three genes of interest (thyroid receptor α, thyroid stimulating hormone, and transthyretin) while BPA only induced thyroid stimulating hormone. In embryos, BDE-47 significantly induced the sodium iodide symporter and thyroid stimulating hormone. TBBPA significantly induced thyroid receptor α and thyroid stimulating hormone, while BPA did not significantly induce any of the genes. Most genes were only induced at the 75% 96 h-LC50 or 96 h-EC50 value; however, thyroid peroxidase and thyroid stimulating hormone demonstrated upregulation in a level as little as the 10% 96 h-LC50 value. The present study provides a new set of data on zebrafish mRNA induction of hypothalamic-pituitary-thyroid genes from exposure to BDE-47, TBBPA, or BPA. This information would serve useful for elucidating the toxicological mechanism of brominated flame retardants, assessing appropriate safety levels in the environment for these compounds, as well as serve as a reference for other man-made contaminants.
我们对斑马鱼（Danio rerio）胚胎-幼虫进行了水基暴露实验，分别暴露于 2,2',4,4'-四溴二苯醚（BDE-47）、四溴双酚 A（TBBPA）或双酚 A（BPA）中，并定量测量了属于下丘脑-垂体-甲状腺（HPT）轴的基因表达，以评估甲状腺功能的不良影响。为了分析 BDE-47、TBBPA 和 BPA 对下丘脑-垂体-甲状腺基因的影响，急性暴露于化学物质的致死浓度下，以确定 96 h-LC50（96 h 致死中浓度）和 96 h-EC50（96 h 有效中浓度）值。然后在亚致死浓度下进行进一步暴露，并提取总 RNA 样品以定量测定感兴趣基因的 mRNA 表达水平。在幼虫中，BDE-47 显著诱导了许多感兴趣的基因，即甲状腺球蛋白、甲状腺过氧化物酶、甲状腺受体 α 和 β、促甲状腺激素和转甲状腺素。TBBPA 仅显著诱导了 3 个感兴趣的基因（甲状腺受体 α、促甲状腺激素和转甲状腺素），而 BPA 仅诱导了促甲状腺激素。在胚胎中，BDE-47 显著诱导了钠碘转运体和促甲状腺激素。TBBPA 显著诱导了甲状腺受体 α 和促甲状腺激素，而 BPA 则没有显著诱导任何基因。大多数基因仅在 96 h-LC50 或 96 h-EC50 值的 75%时被诱导；然而，甲状腺过氧化物酶和促甲状腺激素在低至 96 h-LC50 值的 10%时就被上调。本研究提供了一组关于斑马鱼暴露于 BDE-47、TBBPA 或 BPA 后下丘脑-垂体-甲状腺基因 mRNA 诱导的新数据。这些信息将有助于阐明溴化阻燃剂的毒理学机制，评估这些化合物在环境中的适当安全水平，并为其他人为污染物提供参考。
