Direct effects, compensation, and recovery in female fathead minnows exposed to a model aromatase inhibitor.
BACKGROUND
Several chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis.


OBJECTIVE
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.
U.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
Daniel L
DL
Villeneuve
Nathaniel D
ND
Mueller
Dalma
D
Martinović
Elizabeth A
EA
Makynen
Michael D
MD
Kahl
Kathleen M
KM
Jensen
Elizabeth J
EJ
Durhan
Jenna E
JE
Cavallin
David
D
Bencic
Gerald T
GT
Ankley
D000818:Animals; D047072:Aromatase Inhibitors / Q000032:analysis / Q000633:toxicity*; D003530:Cyprinidae / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000032:analysis / Q000097:blood; D017316:Fadrozole / Q000032:analysis / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006728:Hormones / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000097:blood / Q000378:metabolism; D013739:Testosterone / Q000032:analysis / Q000097:blood; D018675:Toxicity Tests; D014819:Vitellogenins / Q000097:blood / Q000187:drug effects
D047072:Aromatase Inhibitors; D006728:Hormones; D012333:RNA, Messenger; D013256:Steroids; D014819:Vitellogenins; D013739:Testosterone; D004958:Estradiol; D017316:Fadrozole