Abstract：
Although tetrabromobisphenol A (TBBPA) has been well proven to disturb TH signaling in both in vitro and in vivo assays, it is still unclear whether TBBPA can affect brain development due to TH signaling disruption. Here, we employed the T3-induced Xenopus metamorphosis assay (TIXMA) and the spontaneous metamorphosis assay to address this issue. In the TIXMA, 5-500 nmol/L TBBPA affected T3-induced TH-response gene expression and T3-induced brain development (brain morphological changes, cell proliferation, and neurodifferentiation) at premetamorphic stages in a complicated biphasic concentration-response manner. Notably, 500 nmol/L TBBPA treatment alone exerted a stimulatory effect on tadpole growth and brain development at these stages, in parallel with a lack of TH signaling activation, suggesting the involvement of other signaling pathways. As expected, at the metamorphic climax, we observed inhibitory effects of 50-500 nmol/L TBBPA on metamorphic development and brain development, which was in agreement with the antagonistic effects of higher concentrations on T3-induced brain development at premetamorphic stages. Taken together, all results demonstrate that TBBPA can disturb TH signaling and subsequently interfere with TH-dependent brain development in Xenopus; meanwhile, other signaling pathways besides TH signaling could be involved in this process. Our study improves the understanding of the effects of TBBPA on vertebrate brain development.
摘要：
尽管四溴双酚A（TBBPA）已被证明在体外和体内测定中干扰TH信号传导，目前尚不清楚TBBPA是否会由于TH信号中断而影响大脑发育。这里,我们采用了T3诱导的非洲爪狼变态试验(TIXMA)和自发变态试验来解决这个问题.在TIXMA，5-500nmol/LTBBPA影响T3诱导的TH反应基因表达和T3诱导的大脑发育（大脑形态变化，细胞增殖，和神经分化）在变质前阶段以复杂的双相浓度-反应方式进行。值得注意的是,在这些阶段，500nmol/LTBBPA单独处理对t的生长和大脑发育具有刺激作用，在缺乏TH信号激活的同时，提示其他信号通路的参与。不出所料,在变质高潮时,我们观察到50-500nmol/L的TBBPA对变态发育和脑发育的抑制作用，这与较高浓度对变质前阶段T3诱导的大脑发育的拮抗作用一致。一起来看,所有结果表明,TBBPA可以干扰TH信号传导,进而干扰TH依赖性的脑发育;同时,除TH信号外，其他信号通路也可能参与这一过程。我们的研究提高了对TBBPA对脊椎动物大脑发育影响的理解。
