title: Optimization of the T3-induced Xenopus metamorphosis assay for detecting thyroid hormone signaling disruption of chemicals.
abstract: T3-induced Xenopus metamorphosis is an ideal model for detecting thyroid hormone (TH) signaling disruption of chemicals. To optimize the T3-induced Xenopus assay and improve its sensitivity and reproducibility, we intend to develop quantitatively morphological endpoints and choose appropriate concentrations and exposure durations for T3 induction. Xenopus laevis at stage 52 were exposed to series of concentrations of T3 (0.31-2.5nmol/L) for 6days. By comparing morphological changes induced by T3, we propose head area, mouth width, unilateral brain width/brain length, and hindlimb length/snout-vent length as quantitative parameters for characterizing T3-induced morphological changes, with body weight as a parameter for indicating integrated changes. By analyzing time-response curves, we found that following 4-day exposure, T3-induced grossly morphological changes displayed linear concentration-response curves, with moderate morphological changes resulting from 1.25nmol/L T3 exposure. When using grossly morphological endpoints to detect TH signaling disruption, we propose 4days as exposure duration of T3, with concentrations close to 1.25nmol/L as induction concentrations. However, it is appropriate to examine morphological and molecular changes of the intestine on day 2 due to their early response to T3. The quantitative endpoints and T3 induction concentrations and durations we determined would improve the sensitivity and the reproducibility of the T3-induced Xenopus metamorphosis assay.
authors.affiliation: School of Environment and Resource, Southwest University of Science and Technology, Mianyang 621010, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: yao_tykd@sina.com.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yao
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: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Zhang
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.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Environment and Resource, Southwest University of Science and Technology, Mianyang 621010, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Zheng
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: School of Environment and Resource, Southwest University of Science and Technology, Mianyang 621010, China. Electronic address: zqdonger@126.com.
authors.forename: Qingdong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D017252:CD3 Complex / Q000378:metabolism*; D052244:Endocrine Disruptors / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism*; D014981:Xenopus
chemical_list: D017252:CD3 Complex; D052244:Endocrine Disruptors; D013963:Thyroid Hormones
keywords: Disruption; Morphological endpoints; T3 induction; TH-response gene expression; Thyroid hormone signaling; Xenopus laevis