期刊
REPRODUCTIVE TOXICOLOGY
卷 57, 期 -, 页码 10-20出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2015.04.012
关键词
Endocrine disruption; Adverse outcome pathways; Danio rerio; Behaviour; Alternatives to animal testing; Thyroxine; Teratogenic effects; Ecotoxicology
资金
- German Federal Environmental Foundation (DBU)
- DAAD RISE Programme
- Helmholtz Centre for Environmental Research
Craniofacial malformations, reduced locomotion and induction of genes encoding for enzymes involved in thyroid hormone synthesis were assessed using methimazole and N-phenylthiourea in zebrafish embryos. Gene expression, the most sensitive endpoint (EC50.MMI =372-765 mu M, EC50-PTU = 7.6-8.6 mu M), was analysed in wild-type and in a transgenic strain, tg(tg:mCherry), expressing mCherry fluorescence protein under the control of the thyroglobulin gene. Reduction of locomotion and craniofacial malformations were observed at one or two orders of magnitude above concentrations affecting gene expression, respectively. Both effects could be linked to the malformations caused by reduced thyroxin levels. Our results show that due to the presence of the autoregulatory loop of the hypothalamus pituitary thyroid axis, various molecular initiating events of thyroid disruption are amenable for the zebrafish embryo. We propose the tg(tg:mCherry) bioassay as a sensitive tool in medium scale screening of goitrogens, given the minimal effort for sample preparation and analysis of gene expression. (C)2015 Elsevier Inc. All rights reserved.
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