TY - JOUR
T1 - Chemical class-specific gene expression changes in the zebrafish embryo after exposure to glycol ether alkoxy acids and 1,2,4-triazole antifungals
AU - Hermsen, Sanne A. B.
AU - Pronka, Tessa E.
AU - van den Brandhof, Evert-Jan
AU - van der Ven, Leo T. M.
AU - Piersma, Aldert H.
PY - 2011/9
Y1 - 2011/9
N2 - 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 24 h 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.
AB - 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 24 h 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.
KW - Toxicogenomics
KW - Zebrafish embryotoxicity test
KW - Gene expression
KW - Alternative test
KW - Glycol ether
KW - Triazole
U2 - 10.1016/j.reprotox.2011.05.010
DO - 10.1016/j.reprotox.2011.05.010
M3 - Article
C2 - 21621602
VL - 32
SP - 245
EP - 252
JO - Reproductive Toxicology
JF - Reproductive Toxicology
SN - 0890-6238
IS - 2
ER -