| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2593381 | Reproductive Toxicology | 2015 | 11 Pages |
•Goitrogen-induced teratogenicity, gene expression and behavior changes were studied.•Concentration-dependent effects could be shown for all endpoints studied.•Expression changes of TH synthesis genes proved to be the most sensitive endpoint.•Gene expression could be also analysed using a transgenic zebrafish embryo bioassay.•The tg(tg:mCherry) bioassay might be used in medium scale screening of goitrogens.
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 μM, EC50_PTU = 7.6–8.6 μM), 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.
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