State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University , Nanjing, Jiangsu 210023, China.
Environ Sci Technol. 2015 Feb 3;49(3):1823-33. doi: 10.1021/es503833q. Epub 2015 Jan 21.
2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), 6-hydroxy-tetrabromodiphenyl ether (6-OH-BDE-47), and 6-methoxy-tetrabromodiphenyl ether (6-MeO-BDE-47) are the most detected congeners of polybrominated diphenyl ethers (PBDEs), OH-BDEs, and MeO-BDEs, respectively, in aquatic organisms. Although it has been demonstrated that BDE-47 can interfere with certain endocrine functions that are mediated through several nuclear hormone receptors (NRs), most of these findings were from mammalian cell lines exposed in vitro. In the present study, embryos and larvae of zebrafish were exposed to BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 to compare their accumulation, biotransformation, and bioconcentration factors (BCF) from 4 to 120 hpf. In addition, effects on expression of genes associated with eight different pathways regulated by NRs were investigated at 120 hpf. 6-MeO-BDE-47 was most bioaccumulated and 6-OH-BDE-47, which was the most potent BDE, was least bioaccumulated. Moreover, the amount of 6-MeO-BDE-47, but not BDE-47, transformed to 6-OH-BDE-47 increased in a time-dependent manner, approximately 0.01%, 0.04%, and 0.08% at 48, 96, and 120 hpf, respectively. Expression of genes regulated by the aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and mineralocorticoid receptor (MR) was affected in larvae exposed to 6-OH-BDE-47, whereas genes regulated by AhR, ER, and the glucocorticoid receptor (GR) were altered in larvae exposed to BDE-47. The greatest effect on expression of genes was observed in larvae exposed to 6-MeO-BDE-47. Specifically, 6-MeO-BDE-47 affected the expression of genes regulated by AhR, ER, AR, GR, and thyroid hormone receptor alpha (TRα). These pathways were mostly down-regulated at 2.5 μM. Taken together, these results demonstrate the importance of usage of an internal dose to assess the toxic effects of PBDEs. BDE-47 and its analogs elicited distinct effects on expression of genes of different hormone receptor-mediated pathways, which have expanded the knowledge of different mechanisms of endocrine disrupting effects in aquatic vertebrates. Because some of these homologues are natural products, assessments of risks of anthropogenic PBDE need to be made against the background of concentrations from naturally occurring products. Even though PBDEs are being phased out as flame retardants, the natural products remain.
2,2',4,4'-四溴二苯醚 (BDE-47)、6-羟基四溴二苯醚 (6-OH-BDE-47) 和 6-甲氧基四溴二苯醚 (6-MeO-BDE-47) 分别是水生生物中多溴二苯醚 (PBDEs)、OH-BDEs 和 MeO-BDEs 中检测到的最主要同系物。尽管已经证明 BDE-47 可以干扰某些通过几种核激素受体 (NRs) 介导的特定内分泌功能，但这些发现大多来自体外暴露于哺乳动物细胞系的研究。在本研究中，将斑马鱼的胚胎和幼虫暴露于 BDE-47、6-OH-BDE-47 和 6-MeO-BDE-47 中，以比较它们在 4 至 120 hpf 时的积累、生物转化和生物浓缩因子 (BCF)。此外，还在 120 hpf 时研究了与 NRs 调节的 8 种不同途径相关的基因表达的影响。6-MeO-BDE-47 被最有效地生物累积，而最有效的 BDE 6-OH-BDE-47 则被最少地生物累积。此外，6-MeO-BDE-47 的转化量呈时间依赖性增加，6-OH-BDE-47 的转化量分别在 48、96 和 120 hpf 时约为 0.01%、0.04%和 0.08%，而 6-MeO-BDE-47 的转化量增加，而不是 BDE-47。暴露于 6-OH-BDE-47 的幼虫中，受芳香烃受体 (AhR)、雌激素受体 (ER) 和盐皮质激素受体 (MR) 调节的基因表达受到影响，而暴露于 BDE-47 的幼虫中，受 AhR、ER 和糖皮质激素受体 (GR) 调节的基因表达发生改变。暴露于 6-MeO-BDE-47 的幼虫中观察到对基因表达的最大影响。具体而言，6-MeO-BDE-47 影响受 AhR、ER、AR、GR 和甲状腺激素受体 alpha (TRα) 调节的基因表达。这些途径在 2.5 μM 时大多被下调。总的来说，这些结果表明使用内部剂量来评估 PBDEs 的毒性影响的重要性。BDE-47 及其类似物对不同激素受体介导途径的基因表达产生了不同的影响，这扩展了水生脊椎动物内分泌干扰作用不同机制的知识。由于其中一些同源物是天然产物，因此需要在评估人为 PBDE 的风险时考虑到天然产物的浓度。尽管 PBDEs 作为阻燃剂正在逐步淘汰，但天然产物仍然存在。
