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首页> 外文期刊>Environmental Science & Technology >TBBPA and Its Alternatives Disturb the Early Stages of Neural Development by Interfering with the NOTCH and WNT Pathways
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TBBPA and Its Alternatives Disturb the Early Stages of Neural Development by Interfering with the NOTCH and WNT Pathways

机译：TBBPA及其替代品通过干扰NOTCH和WNT途径干扰神经发育的早期阶段

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摘要

Tetrabromobisphenol A (TBBPA), as well as its alternatives Tetrabromobisphenol S (TBBPS) and Tetrachlorobisphenol A (TCBPA), are widely used halogenated flame retardants. Their high detection rates in human breast milk and umbilical cord serum have raised wide concerns about their adverse effects on human fetal development. In this study, we evaluated the cytotoxicity and neural developmental toxicity of TBBPA, TBBPS, and TCBPA with a mouse embryonic stem cell (mESC) system, at human body fluid and environmental relevant doses. All the three compounds showed similar trends in their cytotoxic effects. However, while TBBPA and TBBPS stimulated ESC neural differentiation, TCBPA significantly inhibited neurogenesis. Mechanistically, we demonstrated that, as far as the NOTCH (positive regulator) and WNT (negative regulator) pathways were concerned, TBBPA only partially and slightly disturbed them, whereas TBBPS significantly inhibited the WNT pathway, and TCBPA down-regulated the expression of NOTCH effectors but increased the WNT signaling, actions which both inhibited neural specification. In conclusion, our findings suggest that TBBPS and TCBPA may not be safe alternatives to TBBPA, and their toxicity need to be comprehensively evaluated.
机译：四溴双酚A（TBBPA）及其替代物四溴双酚S（TBBPS）和四氯双酚A（TCBPA）是广泛使用的卤化阻燃剂。它们在人母乳和脐带血清中的高检出率引起了人们对它们对人胎儿发育的不利影响的广泛关注。在这项研究中，我们用人体胚胎干和环境相关剂量的小鼠胚胎干细胞（mESC）系统评估了TBBPA，TBBPS和TCBPA的细胞毒性和神经发育毒性。这三种化合物的细胞毒性作用均显示出相似的趋势。然而，尽管TBBPA和TBBPS刺激了ESC神经分化，但TCBPA显着抑制了神经发生。从机理上讲，我们证明，就NOTCH（正向调节剂）和WNT（负向调节剂）途径而言，TBBPA仅部分或轻微干扰它们，而TBBPS显着抑制WNT途径，而TCBPA下调了NOTCH的表达效应子但增加了WNT信号传导，这些作用均抑制了神经规范。总之，我们的发现表明，TBBPS和TCBPA可能不是TBBPA的安全替代品，它们的毒性需要进行全面评估。

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  • 来源
    《Environmental Science & Technology》 |2018年第9期|5459-5468|共10页
  • 作者

    Nuoya Yin; Shaojun Liang; Shengxian Liang; Renjun Yang; Bowen Hu; Zhanfen Qin; Aifeng Liu; Francesco Faiola;

  • 作者单位

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China;

    CAS Key Laboratory of Bio-based Materials, Qingdao Institute of Biomass Energy and Bioprocess Technology, Chinese Academy of Science, Qingdao 266101, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China,College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China;

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