title: Chemical class-specific gene expression changes in the zebrafish embryo after exposure to glycol ether alkoxy acids and 1,2,4-triazole antifungals.
abstract: The zebrafish embryotoxicity test (ZET) is an alternative test to predict embryotoxicity of substances based on morphological assessment. Implementing transcriptomics may increase sensitivity and objectivity of the test system. We applied the category approach to compare effects of compounds from two chemical classes, the glycol ethers and 1,2,4-triazoles, on the embryo. At 24h post fertilization, microarray analysis revealed several thousands of responsive genes after glycol ether exposure, whereas the triazoles significantly regulated only several hundreds of genes. Principal component analysis of the genes commonly regulated per chemical class demonstrated that the two classes can be distinguished. Gene set enrichment analysis showed that after glycol ether exposure mainly gene sets related to development were downregulated. After triazole exposure, gene sets corresponding to previously described mechanisms of action, such as glycolysis and fatty acid metabolism were regulated. Our results demonstrate that transcriptomics in the ZET provides a more sensitive endpoint than standard morphological assessment. In addition, information about mechanisms of action of substances may become available, thereby facilitating the extrapolation of findings to mammalian species including man.
authors.affiliation: Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Sanne.Hermsen@rivm.nl
authors.forename: Sanne A B
authors.initials: SA
authors.lastname: Hermsen
authors.forename: Tessa E
authors.initials: TE
authors.lastname: Pronk
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: van den Brandhof
authors.forename: Leo T M
authors.initials: LT
authors.lastname: van der Ven
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
mesh_terms: D000085:Acetates / Q000633:toxicity*; D000826:Animal Testing Alternatives; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D005659:Fungicides, Industrial / Q000633:toxicity*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D025341:Principal Component Analysis; D014230:Triazoles / Q000145:classification / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology*
chemical_list: D000085:Acetates; D005659:Fungicides, Industrial; D014230:Triazoles; C034096:ethoxyacetic acid; C013598:methoxyacetic acid; C415326:phenoxyacetic acid