PUBLICATION
Toxicogenomic fin(ger)prints for thyroid disruption AOP refinement and biomarker identification in zebrafish embryos
- Authors
- Reinwald, H., König, A., Ayobahan, S.U., Alvincz, J., Sipos, L., Göckener, B., Böhle, G., Shomroni, O., Hollert, H., Salinas, G., Schäfers, C., Eilebrecht, E., Eilebrecht, S.
- ID
- ZDB-PUB-201218-13
- Date
- 2020
- Source
- The Science of the total environment 760: 143914 (Journal)
- Registered Authors
- Keywords
- AOP refinement, Biomarkers, Ecotoxicogenomics, Thyroid signaling, Zebrafish embryo
- MeSH Terms
-
- Animals
- Biomarkers
- Embryo, Nonmammalian
- Endocrine Disruptors*/toxicity
- Thyroid Gland
- Toxicogenetics
- Water Pollutants, Chemical*/toxicity
- Zebrafish/genetics
- PubMed
- 33333401 Full text @ Sci. Total Environ.
Citation
Reinwald, H., König, A., Ayobahan, S.U., Alvincz, J., Sipos, L., Göckener, B., Böhle, G., Shomroni, O., Hollert, H., Salinas, G., Schäfers, C., Eilebrecht, E., Eilebrecht, S. (2020) Toxicogenomic fin(ger)prints for thyroid disruption AOP refinement and biomarker identification in zebrafish embryos. The Science of the total environment. 760:143914.
Abstract
Endocrine disruption (ED) can trigger far-reaching effects on environmental populations, justifying a refusal of market approval for chemicals with ED properties. For the hazard assessment of ED effects on the thyroid system, regulatory decisions mostly rely on amphibian studies. Here, we used transcriptomics and proteomics for identifying molecular signatures of interference with thyroid hormone signaling preceding physiological effects in zebrafish embryos. For this, we analyzed the thyroid hormone 3,3',5-triiodothyronine (T3) and the thyroid peroxidase inhibitor 6-propyl-2-thiouracil (6-PTU) as model substances for increased and repressed thyroid hormone signaling in a modified zebrafish embryo toxicity test. We identified consistent gene expression fingerprints for both modes-of-action (MoA) at sublethal test concentrations. T3 and 6-PTU both significantly target the expression of genes involved in muscle contraction and functioning in an opposing fashion, allowing for a mechanistic refinement of key event relationships in thyroid-related adverse outcome pathways in fish. Furthermore, our fingerprints identify biomarker candidates for thyroid disruption hazard screening approaches. Perspectively, our findings will promote the AOP-based development of in vitro assays for thyroidal ED assessment, which in the long term will contribute to a reduction of regulatory animal tests.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping