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在暴露于多溴二苯醚代谢物 6-OH-BDE-47 的斑马鱼胚胎(Danio rerio)中,增加的线圈频率与大脑中的细胞凋亡和甲状腺信号改变有关。

Increased coiling frequency linked to apoptosis in the brain and altered thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE metabolite 6-OH-BDE-47.

机构信息

Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, Collage of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, 028000, China.

School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

出版信息

Chemosphere. 2018 May;198:342-350. doi: 10.1016/j.chemosphere.2018.01.081. Epub 2018 Feb 3.

Abstract

Polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants that are ubiquitously detected in the environment and associated with adverse health outcomes. 6-OH-BDE-47 is a metabolite of the flame retardant, 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), and there is increasing concern regarding its developmental neurotoxicity and endocrine disrupting properties. In this study, we report that early life exposure in zebrafish (Danio rerio) embryos to 6-OH-BDE-47 (50 and 100 nM) resulted in higher coiling frequency and significantly increased apoptotic cells in the brain. These effects were partially rescued by overexpression of thyroid hormone receptor β (THRβ) mRNA. Moreover, exposure to 100 nM 6-OH-BDE-47 significantly reduced the number of hypothalamic 5-hydroxytryptamine (5-HT, serotonin)-immunoreactive (5-HT-ir) neurons and the mRNA expression of tryptophan hydroxylase 2 (TPH2). These results indicate that 6-OH-BDE-47 affected thyroid hormone regulation through THRβ and negatively impacted the nervous system, in turn, affecting coiling behavior. Correlations of these endpoints suggest that coiling frequency could be used as an indicator of neurotoxicity in embryos.

摘要

多溴联苯醚(PBDEs)是一组溴化阻燃剂,广泛存在于环境中,并与不良健康结果相关联。6-OH-BDE-47 是阻燃剂 2,2',4,4'-四溴二苯醚(BDE-47)的代谢产物,人们越来越关注其发育神经毒性和内分泌干扰特性。在这项研究中,我们报告了 6-OH-BDE-47(50 和 100nM)在斑马鱼胚胎中的早期生命暴露导致了更高的卷曲频率,并显著增加了大脑中的凋亡细胞。这些影响部分通过甲状腺激素受体 β(THRβ)mRNA 的过表达得到挽救。此外,暴露于 100nM 6-OH-BDE-47 显著减少了下丘脑 5-羟色胺(5-HT,血清素)免疫反应性(5-HT-ir)神经元的数量和色氨酸羟化酶 2(TPH2)的 mRNA 表达。这些结果表明,6-OH-BDE-47 通过 THRβ 影响甲状腺激素调节,并对神经系统产生负面影响,从而影响卷曲行为。这些终点的相关性表明,卷曲频率可作为胚胎神经毒性的指标。

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