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| Status |
Public on Feb 07, 2008 |
| Title |
Triazole Antifungal Toxicogenomics: Iconix3_Triazoles |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver from Sprague Dawley rats dosed with myclobutanil (300 mg/kg/day), propiconazole (300 mg/kg/day), or triadimefon (175 mg/kg/day) for 72 hours. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism and fatty acid metabolism were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis.
Keywords: comparative toxicogenomics
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| Overall design |
A total of 12 liver samples were analyzed. Three biological replicates each for the controls, 300 mg/kg/day myclobutanil, 300 mg/kg/day propiconazole, and 175 mg/kg/day triadimefon.
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| Contributor(s) |
Dix DJ, Goetz AK |
| Citation(s) |
19409404 |
| Submission date |
Feb 06, 2008 |
| Last update date |
Jul 31, 2017 |
| Contact name |
David Dix |
| E-mail(s) |
dix.david@epa.gov
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| Phone |
919-541-2701
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| Organization name |
US EPA
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| Department |
ORD/NCCT
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| Street address |
109 TW Alexander Drive
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| City |
Research Triangle Park |
| State/province |
NC |
| ZIP/Postal code |
27711 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA108049 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10409_RAW.tar |
32.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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