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Altered gene expression in the brain and liver of female fathead minnows Pimephales promelas Rafinesque exposed to fadrozole

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The fathead minnow Pimephales promelas is a small fish species widely used for ecotoxicology research and regulatory testing in North America. This study used a 2000 gene oligonucleotide microarray to evaluate the effects of the aromatase inhibitor, fadrozole, on gene expression in the liver and brain tissue of exposed females. Reproductive measures, plasma vitellogenin and gene expression data for the brain isoform of aromatase (cytP19B), vitellogenin precursors and transferrin provided evidence supporting the efficacy of the fadrozole exposure. Unsupervised analysis of the microarray results identified 20 genes in brain and 41 in liver as significantly up-regulated and seven genes in brain and around 45 in liver as significantly down-regulated. Differentially expressed genes were associated with a broad spectrum of biological functions, many with no obvious relationship to aromatase inhibition. However, in brain, fadrozole exposure elicited significant up-regulation of several genes involved in the cholesterol synthesis, suggesting it as a potentially affected pathway. Gene ontology-based analysis of expression changes in liver suggested overall down-regulation of protein biosynthesis. While real-time polymerase chain reaction analyses supported some of the microarray responses, others could not be verified. Overall, results of this study provide a foundation for developing novel hypotheses regarding the system-wide effects of fadrozole, and other chemical stressors with similar modes of action, on fish biology.

Keywords: aromatase inhibitor; cholesterol; endocrine disruption; fish; transcriptomics; vitellogenin

Document Type: Regular Paper


Affiliations: 1: US EPA, ORD, NERL, Ecological Exposure Research Division, 26 West Martin Luther King Drive, Cincinnati, OH 45268, U.S.A. 2: Pacific Northwest National Laboratory, P. O. Box 999, MSID K3-61, Richland, WA 99352, U.S.A. 3: EcoArray, 12085 Research Drive, Alachua, FL 32615, U.S.A. 4: Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, P. O. Box 110885, Gainesville, FL 32611, U.S.A. 5: US EPA, ORD, NHEERL, Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN 55804, U.S.A.

Publication date: 2008-06-01

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