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Environ Health Perspect. 2009 Apr;117(4):624-31. doi: 10.1289/ ehp.11891. Epub 2008 Dec 12.

Direct effects, compensation, and recovery in female fathead minnows exposed to a model aromatase inhibitor.

Author information

  • 1U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, Duluth, Minnesota 55804, USA. villeneuve.dan@epa.gov

Abstract

BACKGROUND:

Several chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis.

OBJECTIVES:

The objective of this study was to provide a detailed characterization of molecular and biochemical responses of female fathead minnows to a model aromatase inhibitor, fadrozole (FAD).

METHODS:

Fish were exposed via water to 0, 3, or 30 microg FAD/L for 8 days and then held in clean water for 8 days, with samples collected at four time points during each 8-day period. We quantified ex vivo steroid production, plasma steroids, and plasma vitellogenin (Vtg) concentrations and analyzed relative transcript abundance of 10 key regulatory genes in ovaries and 3 in pituitary tissue by real-time polymerase chain reaction.

RESULTS:

Ex vivo 17beta-estradiol (E2) production and plasma E2 and Vtg concentrations were significantly reduced after a single day of exposure to 3 microg or 30 microg FAD/L. However, plasma E2 concentrations recovered by the eighth day of exposure in the 3-microg/L group and within 1 day of cessation of exposure in the 30-microg/L group, indicating concentration- and time-dependent physiologic compensation and recovery. Concentration-dependent increases in transcripts coding for aromatase (A isoform), cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, and follicle-stimulating hormone receptor all coincided with increased E2 production and recovery of plasma E2 concentrations.

CONCLUSIONS:

Results of this research highlight the need to consider compensation/adaptation and recovery when developing and interpreting short-term bioassays or biomarkers or when trying to predict the effects of chemical exposures based on mode of action.

KEYWORDS:

adaptation; endocrine disruption; estradiol; fadrozole; fish; gene expression; reproduction; steroid biosynthesis; vitellogenin

PMID:
19440503
[PubMed - indexed for MEDLINE]
PMCID:
PMC2679608
Free PMC Article
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