Comparative analysis of goitrogenic effects of phenylthiourea and methimazole in zebrafish embryos
Copyright © 2015 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57 |
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| Enthalten in: |
Reproductive toxicology (Elmsford, N.Y.) - 57(2015) vom: 12. Nov., Seite 10-20 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fetter, Eva [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.05.2016 Date Revised 25.08.2015 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.reprotox.2015.04.012 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM248901346 |
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| 245 | 1 | 0 | |a Comparative analysis of goitrogenic effects of phenylthiourea and methimazole in zebrafish embryos |
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| 500 | |a Date Revised 25.08.2015 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Adverse outcome pathways | |
| 650 | 4 | |a Alternatives to animal testing | |
| 650 | 4 | |a Behaviour | |
| 650 | 4 | |a Danio rerio | |
| 650 | 4 | |a Ecotoxicology | |
| 650 | 4 | |a Endocrine disruption | |
| 650 | 4 | |a Teratogenic effects | |
| 650 | 4 | |a Thyroxine | |
| 650 | 7 | |a Antithyroid Agents |2 NLM | |
| 650 | 7 | |a Teratogens |2 NLM | |
| 650 | 7 | |a Methimazole |2 NLM | |
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| 700 | 1 | |a Baldauf, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Da Fonte, Dillon F |e verfasserin |4 aut | |
| 700 | 1 | |a Ortmann, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Scholz, Stefan |e verfasserin |4 aut | |
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