title: Re-evaluation of thyroid hormone signaling antagonism of tetrabromobisphenol A for validating the T3-induced Xenopus metamorphosis assay.
abstract: We developed the T3-induced Xenopus metamorphosis assay, which is supposed to be able to sensitively detect thyroid hormone (TH) signaling disruption of chemicals. The present study aimed to validate the T3-induced Xenopus metamorphosis assay by re-evaluating the TH signaling antagonism of tetrabromobisphenol A (TBBPA), a known TH signaling disruptor. According to the assay we developed, Xenopus tadpoles at stage 52 were exposed to 10-500nmol/L TBBPA in the presence of 1nmol/L T3. After 96hr of exposure, TBBPA in the range of 10-500nmol/L was found to significantly inhibit T3-induced morphological changes of Xenopus tadpoles in a concentration-dependent manner in term of body weight and four morphological endpoints including head area (HA), mouth width (MW), unilateral brain width/brain length (ULBW/BL), and hind-limb length/snout-vent length (HLL/SVL). The results show that these endpoints we developed are sensitive for characterizing the antagonistic effects of TBBPA on T3-induced metamorphosis. Following a 24-hr exposure, we found that TBBPA antagonized expression of T3-induced TH-response genes in the tail, which is consistent with previous findings in the intestine. We propose that the tail can be used as an alternative tissue to the intestine for examining molecular endpoints for evaluating TH signaling disruption. In conclusion, our results demonstrate that the T3-induced Xenopus metamorphosis assay we developed is an ideal in vivo assay for detecting TH signaling disruption.
authors.affiliation: College of Environment, Nanjing University of Technology, Nanjing 211816, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: qinzhanfen@rcees.ac.cn.
authors.forename: Zhanfen
authors.initials: Z
authors.lastname: Qin
authors.affiliation: College of Environment, Nanjing University of Technology, Nanjing 211816, China. Electronic address: wjwei@njut.edu.cn.
authors.forename: Wuji
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D052244:Endocrine Disruptors; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015386:Hazardous Substances / Q000633:toxicity*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism*; D014981:Xenopus / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D052244:Endocrine Disruptors; D015386:Hazardous Substances; D011075:Polybrominated Biphenyls; D013963:Thyroid Hormones; D014284:Triiodothyronine; C020806:tetrabromobisphenol A
keywords: T3 induction; Tetrabromobisphenol A; Thyroid hormone signaling; Xenopus metamorphosis; tail