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Direct Effects, Compensation, and Recovery in Female Fathead Minnows Exposed to the Aromatase Inhibitor Fadrozole
Citation:
VILLENEUVE, D. L., N. D. MUELLER, D. MARTINOVIC, E. A. MAKYNEN, M. D. KAHL, K. M. JENSEN, E. J. DURHAN, J. E. CAVALLIN, D. C. BENCIC, AND G. T. ANKLEY. Direct Effects, Compensation, and Recovery in Female Fathead Minnows Exposed to the Aromatase Inhibitor Fadrozole. Presented at SETAC North America, 29th Annual Meeting, Tampa, FL, November 16 - 20, 2008.
Impact/Purpose:
The objective of this study was to provide a detailed characterization of the molecular and biochemical responses of female fathead minnows to a model aromatase inhibitor, fadrozole.
Description:
A variety of chemicals present in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis. The objective of this study was to provide a detailed characterization of the molecular and biochemical responses of female fathead minnows to a model aromatase inhibitor, fadrozole. Fish were exposed via water to 0, 3, or 30 µg fadrozole/L for 8 d and then held in clean water over an 8 d recovery period, with samples collected at four time points during each 8 d period. Ex vivo steroid production, plasma steroids, and plasma vitellogenin (Vtg) concentrations were quantified and relative transcript abundance of 10 key regulatory genes in ovaries and three in pituitary tissue was analyzed by real-time polymerase chain reaction. Ex vivo 17ß-estradiol (E2) production and plasma E2 and Vtg concentrations were significantly reduced after a single day of exposure to 3 or 30 µg fadrozole/L. However, plasma E2 concentrations recovered by the eighth day of exposure in the 3 µg/L group and within 1 d of cessation of exposure in the 30 µg/L group, indicating concentration-and time-dependent physiological 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. Results of this research highlight the need to consider compensation/adaptation and recovery in evaluating the overall risks associated with the exposure of vertebrate organims to aromatase inhibitors and other endocrine disrupting chemicals.