Tetrabromobisphenol A Disrupts Vertebrate Development via Thyroid Hormone Signaling Pathway in a Developmental Stage-Dependent Manner
Tetrabromobisphenol A Disrupts Vertebrate Development via Thyroid Hormone Signaling Pathway in a Developmental Stage-Dependent Manner
复制标题
四溴双酚 A 通过甲状腺激素信号通路以发育阶段依赖的方式破坏脊椎动物的发育
DOI：
10.1021/es502366g
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发表时间：
2014-07-15
影响因子：
11.4
通讯作者：
Li, Jian-Zhong
中科院分区：
文献类型：
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作者：
Zhang, Yin-Feng;Xu, Wei;Li, Jian-Zhong
四溴双酚A（TBBPA）对甲状腺激素（TH）依赖的脊椎动物发育的影响的数据是有限的，虽然TBBPA已被证明在体外破坏TH信号通路在转录水平。在这项研究中，我们研究了TBBPA对T3诱导的和自发的非洲爪蟾变态的影响，这与高等脊椎动物中TH依赖的发育有许多相似之处。在为期6天的T3诱导的变态试验中，使用premetamorphic蝌蚪，10-1000 nM TBBPA表现出抑制作用T3诱导的TH-反应基因的表达和形态变化的浓度依赖性的方式，与弱刺激作用蝌蚪发育和TH-反应基因的表达在T3诱导的情况下。在自发变态试验中，我们进一步发现TBBPA促进了蝌蚪从S1期到56期（前变态期和原变态期）的发育，但抑制了从57期到66期（变态顶极）的变态发育。这些结果有力地表明，TBBPA，即使在低浓度下，也以发育阶段依赖性的方式破坏TH依赖性发育，即，TBBPA在动物具有高内源性TH水平的发育阶段表现出拮抗活性，而在动物具有低内源性TH水平的发育阶段，TBBPA充当激动剂。我们的研究强调了TBBPA对脊椎动物TH依赖性发育的不利影响。
Data concerning effects of tetrabromobisphenol A (TBBPA) on thyroid hormone (TH)-dependent vertebrate development have been limited, although TBBPA has been demonstrated in vitro to disrupt the TH signaling pathway at the transcriptional level. In this study, we investigated the effects of TBBPA on T3-induced and spontaneous Xenopus laevis metamorphosis, which share many similarities with TH-dependent development in higher vertebrates. In a 6-day T3-induced metamorphosis assay using premetamorphic tadpoles, 10-1000 nM TBBPA exhibited inhibitory effects on T3-induced expression of TH-response genes and morphological changes in a concentration-dependent manner, with a weak stimulatory action on tadpole development and TH-response gene expression in the absence of T3 induction. In a spontaneous metamorphosis assay, we further found that TBBPA promoted tadpole development from stage SI to 56 (pre- and prometamorphic stages) but inhibited metamorphic development from stage 57 to 66 (metamorphic climax). These results strongly show that TBBPA, even at low concentrations, disrupts TH-dependent development in a developmental stage-dependent manner, i.e., TBBPA exhibits an antagonistic activity at the developmental stages when animals have high endogenous TH levels, whereas it acts as an agonist at the developmental stages when animals have low endogenous TH levels. Our study highlights the adverse influences of TBBPA on TH-dependent development in vertebrates.