NDLI: Altered gene expression in the brain and ovaries of zebrafish (Danio rerio) exposed to the aromatase inhibitor fadrozole: microarray analysis and hypothesis generation.

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Altered gene expression in the brain and ovaries of zebrafish (Danio rerio) exposed to the aromatase inhibitor fadrozole: microarray analysis and hypothesis generation.

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Altered gene expression in the brain and ovaries of zebrafish (Danio rerio) exposed to the aromatase inhibitor fadrozole: microarray analysis and hypothesis generation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Villeneuve, L. Wang, Rong-Lin Bencic, David C. Biales, Adam D. Martinovic, Dalma Lazorchak, James M. Toth, Gregory Ankley, Gerald T.
Description	Country affiliation: United States Author Affiliation: Villeneuve L ( U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesosta 55804, USA. villeneuve.dan@epa.gov)
Abstract	As part of a research effort examining system-wide responses of the hypothalamic-pituitary-gonadal (HPG) axis in fish to endocrine-active chemicals (EACs) with different modes of action, zebrafish (Danio rerio) were exposed to 25 or 100 microg/L of the aromatase inhibitor fadrozole for 24, 48, or 96 h. Global transcriptional response in brain and ovarian tissue of fish exposed to 25 microg/L of fadrozole was compared to that in control fish using a commercially available, 22,000-gene oligonucleotide microarray. 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. Promoter motif analysis identified GATA-binding factor 2, Ikaros 2, alcohol dehydrogenase gene regulator 1, myoblast-determining factor, and several heat shock factors as being associated with coexpressed gene clusters that were differentially expressed following exposure to fadrozole. Based on the transcriptional changes observed, it was hypothesized that fadrozole elicits neurodegenerative stress in brain tissue and that fish cope with this stress through proliferation of radial glial cells. Additionally, it was hypothesized that changes of gene expression in the ovary of fadrozole-exposed zebrafish reflect disruption of oocyte maturation and ovulation because of impaired vitellogenesis. These hypotheses and others derived from the microarray results provide a foundation for future studies aimed at understanding responses of the HPG axis to EACs and other chemical stressors.
File Format	HTM / HTML
ISSN	07307268
Issue Number	8
Volume Number	28
e-ISSN	15528618
Journal	Environmental Toxicology and Chemistry
Language	English
Publisher	Wiley
Publisher Date	2009-08-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Research Support, U.s. Gov't, Non-p.h.s. Brain Fadrozole Promoter Regions, Genetic Toxicity Discipline Environmental Health Gene Expression Regulation Discipline Toxicology Male Zebrafish Gene Expression Profiling Metabolism Drug Effects Journal Article Aromatase Inhibitors Ovary Animals Protein Array Analysis Discipline Chemistry Female
Content Type	Text
Resource Type	Article
Subject	Environmental Chemistry Health, Toxicology and Mutagenesis

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