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Altered Gene Expression in the Brain and Ovaries of Zebrafish Exposed to the Aromatase Inhibitor Fadrosole: Microarray Analysis for Hypothesis Generation
Citation:
VILLENEUVE, D. L., R. WANG, D. C. BENCIC, A. D. BIALES, D. MARTINOVIC, J. M. LAZORCHAK, G. P. TOTH, AND G. T. ANKLEY. Altered Gene Expression in the Brain and Ovaries of Zebrafish Exposed to the Aromatase Inhibitor Fadrosole: Microarray Analysis for Hypothesis Generation. Presented at 35th Annual Aquatic Toxicity Workshop, Saskatoon, SK, CANADA, October 05 - 08, 2008.
Impact/Purpose:
Based on the transcriptional changes observed, we hypothesized that exposure to fadrozole elicits neurodegenerative stress and that fish cope with that stress through proliferation of radial glial cells. Additionally, we hypothesize that gene expression changes in the ovary of fadrozole-exposed zebrafish reflect disruption of oocyte maturation and ovulation due to impaired vitellogenesis.
Description:
A part of an overall program of research aimed at examining system-wide responses of the hypothalamic-pituitary-gonadal axis in fish to endocrine active chemicals acting through a variety of modes of action, we exposed zebrafish (Danio rerio) to the aromatase inhibitor fadrozole for 24, 48, or 96 h. Global transcriptional response in brain and ovary tissue was examined using a commercially available 22,000 gene oligonucleotide microarray. Exposure to fadrozole altered expression of approximately 1200 transcripts in ovary and 1000 transcripts in brain. Transcripts altered in brain were functionally linked to differentiation, development, DNA replication, and cell cycle. Additionally, multiple genes associated with the one carbon pool by folate pathway (KEGG 00670) were significantly up-regulated. Transcripts altered in ovary were functionally linked to cell-cell adhesion, extracellular matrix, vasculogenesis, and development. Based on the transcriptional changes observed, we hypothesized that exposure to fadrozole elicits neurodegenerative stress and that fish cope with that stress through proliferation of radial glial cells. Additionally, we hypothesize that gene expression changes in the ovary of fadrozole-exposed zebrafish reflect disruption of oocyte maturation and ovulation due to impaired vitellogenesis.