Transcriptomics

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Transcription profiling of rat - triazole antifungal toxicogenomics: rat_repro_Liver


ABSTRACT: 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 and testis from Wistar Han IGS rats fed myclobutanil (M: 500, 2000 ppm), propiconazole (P: 500, 2500 ppm), or triadimefon (T: 500, 1800 ppm) from gestation day six to postnatal day 92. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Triadimefon induced a distinctive expression profile of genes involved in liver sterol biosynthesis. There were no common pathways modulated by all three triazoles in the testis. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pc, Ppap2b), and steroid metabolism (Srd5a1, Ugt1a1, Ugt2a1) 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, sterol biosynthesis, and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 35 liver samples were analyzed. Seven biological replicates for the controls, 5 biological replicates for mid dose myclobutanil and 5 biological replicates for high dose mylcobutanil. There are 5 biological replicates for mid dose propiconazole, 4 biological replicates for high dose propiconazole, 5 biological replicates for mid dose triadimefon, and 4 biological replicates for triadimefon.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Rattus norvegicus  

SUBMITTER: David Dix  

PROVIDER: E-GEOD-10411 | ArrayExpress | 2008-04-09

SECONDARY ACCESSION(S): GSE10411PRJNA108053

REPOSITORIES: GEO, ArrayExpress

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