title: Tetrabromobisphenol A disrupts vertebrate development via thyroid hormone signaling pathway in a developmental stage-dependent manner.
abstract: 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 51 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.
authors: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences and ‡Department of Environmental Bio-Technology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences , P.O. Box 2871, Beijing 100085, China.
authors: Yin-Feng
authors: YF
authors: Zhang
authors: Wei
authors: W
authors: Xu
authors: Qin-Qin
authors: QQ
authors: Lou
authors: Yuan-Yuan
authors: YY
authors: Li
authors: Ya-Xian
authors: YX
authors: Zhao
authors: Wu-Ji
authors: WJ
authors: Wei
authors: Zhan-Fen
authors: ZF
authors: Qin
authors: Hui-Li
authors: HL
authors: Wang
authors: Jian-Zhong
authors: JZ
authors: Li
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006614:Hindlimb / Q000033:anatomy & histology; D007422:Intestines / Q000187:drug effects / Q000254:growth & development; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008018:Life Cycle Stages / Q000187:drug effects* / Q000235:genetics; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology; D014982:Xenopus laevis / Q000235:genetics / Q000254:growth & development*
chemical_list: D011075:Polybrominated Biphenyls; D013963:Thyroid Hormones; D014284:Triiodothyronine; C020806:tetrabromobisphenol A