Concentration-response analysis of differential gene expression in the zebrafish embryotoxicity test following flusilazole exposure
- Authors
- Hermsen, S.A., Pronk, T.E., van den Brandhof, E.J., van der Ven, L.T., and Piersma, A.H.
- ID
- ZDB-PUB-120306-10
- Date
- 2012
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 127(1): 303-312 (Journal)
- Registered Authors
- van der Ven, Leo
- Keywords
- zebrafish embryotoxicity test, toxicogenomics, concentration-response, alternative test, flysilazole, triazole
- MeSH Terms
-
- Abnormalities, Drug-Induced/etiology
- Abnormalities, Drug-Induced/pathology
- Animal Testing Alternatives
- Animals
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects*
- Fungicides, Industrial/classification
- Fungicides, Industrial/toxicity*
- Gene Expression/drug effects*
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/drug effects*
- Oligonucleotide Array Sequence Analysis
- RNA, Messenger/metabolism
- Sensitivity and Specificity
- Silanes/classification
- Silanes/toxicity*
- Teratogens/classification
- Teratogens/toxicity*
- Triazoles/classification
- Triazoles/toxicity*
- Zebrafish
- PubMed
- 22382673 Full text @ Toxicol. Sci.
- CTD
- 22382673
The zebrafish embryotoxicity test (ZET) is considered as a promising alternative model in predictive toxicology. Currently, morphological assessment of the embryo is the main readout for this assay. However, implementation of transcriptomics may help to detect more subtle effects which may increase the sensitivity and predictability of the test. In this study, we tested a concentration-response of flusilazole in the ZET. After exposure for 24 hours post fertilization, microarray analysis revealed a number of processes to be regulated in a concentration-dependent way. We identified development related processes, retinol metabolism and transcription, as well as processes corresponding to the anti-fungal mechanism of action, steroid biosynthesis and fatty acid metabolism, to be differentially regulated. Retinol metabolism and transcription were already significantly altered at concentrations that were not inducing morphological effects. Differential expression of genes related to steroid biosynthesis and fatty acid metabolism showed a concentration-response similar to morphological response. An increase in concentration was also positively associated with an increase in magnitude of expression for individual genes within functional processes. Our study shows that transcriptomics analysis in the ZET is a more sensitive readout of compound-induced effects than morphological assessment. However, the interpretation of differential gene expression in terms of predicting morphological effects is not straightforward and requires further study.