title: Comparative analysis of goitrogenic effects of phenylthiourea and methimazole in zebrafish embryos.
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.
authors.affiliation: Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany. Electronic address: fettervica@gmail.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Fetter
authors.affiliation: Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Baldauf
authors.affiliation: Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany; Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, 20 Marie-Curie, K1N 6N5 Ottawa, ON, Canada.
authors.forename: Dillon F
authors.initials: DF
authors.lastname: Da Fonte
authors.affiliation: Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ortmann
authors.affiliation: Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity*; D019465:Craniofacial Abnormalities / Q000139:chemically induced; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008713:Methimazole / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D010670:Phenylthiourea / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*; D013974:Thyroxine / Q000494:pharmacology; D015027:Zebrafish / Q000002:abnormalities / Q000235:genetics / Q000502:physiology
chemical_list: D013956:Antithyroid Agents; D013723:Teratogens; D008713:Methimazole; D010670:Phenylthiourea; D013974:Thyroxine
keywords: Adverse outcome pathways; Alternatives to animal testing; Behaviour; Danio rerio; Ecotoxicology; Endocrine disruption; Teratogenic effects; Thyroxine