PUBLICATION
Comparative analysis of goitrogenic effects of phenylthiourea and methimazole in zebrafish embryos
- Authors
- Fetter, E., Baldauf, L., Da Fonte, D.F., Ortmann, J., Scholz, S.
- ID
- ZDB-PUB-150513-15
- Date
- 2015
- Source
- Reproductive toxicology (Elmsford, N.Y.) 57: 10-20 (Journal)
- Registered Authors
- Keywords
- Danio rerio, adverse outcome pathways, alternatives to animal testing, behaviour, ecotoxicology, endocrine disruption, teratogenic effects, thyroxine
- MeSH Terms
-
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/physiology
- Zebrafish/abnormalities
- Zebrafish/genetics
- Zebrafish/physiology
- Thyroxine/pharmacology
- Teratogens/toxicity*
- Phenylthiourea/toxicity*
- Craniofacial Abnormalities/chemically induced
- Antithyroid Agents/toxicity*
- Motor Activity/drug effects
- Animals
- Methimazole/toxicity*
- Gene Expression Regulation, Developmental/drug effects*
- PubMed
- 25962731 Full text @ Reprod. Toxicol.
- CTD
- 25962731
Citation
Fetter, E., Baldauf, L., Da Fonte, D.F., Ortmann, J., Scholz, S. (2015) Comparative analysis of goitrogenic effects of phenylthiourea and methimazole in zebrafish embryos. Reproductive toxicology (Elmsford, N.Y.). 57:10-20.
Abstract
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=372-765μM, EC50_PTU=7.6-8.6μM), 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping