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.
Villeneuve
Daniel L
DL
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
Mueller
Nathaniel D
ND
Martinović
Dalma
D
Makynen
Elizabeth A
EA
Kahl
Michael D
MD
Jensen
Kathleen M
KM
Durhan
Elizabeth J
EJ
Cavallin
Jenna E
JE
Bencic
David
D
Ankley
Gerald T
GT
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