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十溴二苯醚(BDE-209)的生物浓缩和代谢导致斑马鱼幼鱼甲状腺内分泌紊乱。

Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae.

机构信息

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

出版信息

Aquat Toxicol. 2012 Apr;110-111:141-8. doi: 10.1016/j.aquatox.2012.01.008. Epub 2012 Jan 18.

DOI:10.1016/j.aquatox.2012.01.008
PMID:22307006
Abstract

Polybrominated diphenyl ethers (PBDEs) have the potential to disturb the thyroid endocrine system, but little is known of such effects or underlying mechanisms of BDE-209 in fish. In the present study, bioconcentration and metabolism of BDE-209 were investigated in zebrafish embryos exposed at concentrations of 0, 0.08, 0.38 and 1.92 mg/L in water until 14 days post-fertilization (dpf). Chemical analysis revealed that BDE-209 was accumulated in zebrafish larvae, while also metabolic products were detected, including octa- and nona-BDEs, with nona-BDEs being predominant. The exposure resulted in alterations of both triiodothyronine (T3) and thyroxine (T4) levels, indicating thyroid endocrine disruption. Gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis was further examined, and the results showed that the genes encoding corticotrophin-releasing hormone (CRH) and thyroid-stimulating hormone (TSHβ) were transcriptionally significantly up-regulated. Genes involved in thyroid development (Pax8 and Nkx2.1) and synthesis (sodium/iodide symporter, NIS, thyroglobulin, TG) were also transcriptionally up-regulated. Up-regulation of mRNA for thyronine deiodinase (Dio1 and Dio2) and thyroid hormone receptors (TRα and TRβ) was also observed. However, the genes encoding proteins involved in TH transport (transthyretin, TTR) and metabolism (uridinediphosphate-glucuronosyl-transferase, UGT1ab) were transcriptionally significantly down-regulated. Furthermore, protein synthesis of TG was significantly up-regulated, while that of TTR was significantly reduced. These results suggest that the hypothalamic-pituitary-thyroid axis can be evaluated to determine thyroid endocrine disruption by BDE-209 in developing zebrafish larvae.

摘要

多溴联苯醚(PBDEs)有可能扰乱甲状腺内分泌系统,但对鱼类中 BDE-209 的这种影响或潜在机制知之甚少。在本研究中,研究了 BDE-209 在斑马鱼胚胎中的生物浓缩和代谢情况,这些胚胎在水中暴露于 0、0.08、0.38 和 1.92 mg/L 的浓度下,直到受精后 14 天(dpf)。化学分析表明,BDE-209 在斑马鱼幼虫中积累,同时也检测到代谢产物,包括八溴和九溴代 BDE,其中九溴代 BDE 占主导地位。暴露导致三碘甲状腺原氨酸(T3)和甲状腺素(T4)水平发生变化,表明甲状腺内分泌失调。进一步检查了下丘脑-垂体-甲状腺(HPT)轴中的基因转录,结果表明,促皮质素释放激素(CRH)和促甲状腺激素(TSHβ)的编码基因转录显著上调。参与甲状腺发育(Pax8 和 Nkx2.1)和合成(钠/碘同向转运体,NIS,甲状腺球蛋白,TG)的基因也转录上调。甲状腺素脱碘酶(Dio1 和 Dio2)和甲状腺激素受体(TRα 和 TRβ)的 mRNA 也上调。然而,参与 TH 转运(转甲状腺素蛋白,TTR)和代谢(尿苷二磷酸-葡萄糖醛酸转移酶,UGT1ab)的蛋白质编码基因转录显著下调。此外,TG 的蛋白质合成显著上调,而 TTR 的蛋白质合成显著降低。这些结果表明,通过 BDE-209 对发育中的斑马鱼幼虫进行下丘脑-垂体-甲状腺轴的评估可以确定甲状腺内分泌失调。

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