You are here:
Effects of antiandrogen flutamide on steroidogenesis and gene expression in female fathead minnow ovary
Citation:
Milsk, R., Dan Villeneuve, A. Schroeder, E. Perkins, N. Garcia-Reyero, AND G. Ankley. Effects of antiandrogen flutamide on steroidogenesis and gene expression in female fathead minnow ovary. MWSETAC/SOT Meeting, Duluth, MN, March 09 - 11, 2015.
Impact/Purpose:
not applicable
Description:
Mechanisms underlying reproductive impacts of antiandrogens in fish are not well-characterized and effective biomarkers of antiandrogen exposure are lacking. This work sought to identify genes and pathways affected by antiandrogen exposure in the fathead minnow (Pimephales promelas), and compare these to previous results for zebrafish (Danio rerio). A time-course study with exposure to flutamide, an antiandrogenic pharmaceutical, was conducted with female fathead minnows. Sexually mature fish were exposed to flutamide (50 or 500 µg/L) for up to 8 d followed by a recovery period in control water. Fish were sampled after 1, 2, 4, and 8 d of both exposure and recovery. Plasma and ex vivo steroid concentrations were determined, and changes in gene expression in ovary tissue were evaluated within and across time-points using quantitative real-time polymerase chain reaction and a custom 15K fathead minnow microarray. Ex vivo estradiol and testosterone, and plasma estradiol levels were significantly reduced in fish exposed to 500 µg/L flutamide for 2 d. When microarray gene expression data were pooled across 2 and 4 d time points and across flutamide concentration level, 455 significantly altered (=1.3 fold change relative to controls, P<0.05) genes were detected. Of these, only four genes were in common with those reported to be altered in female zebrafish. However, based on Ingenuity Pathway Analysis of the 455 differentially-expressed genes, there were some similarities in enriched canonical pathways between flutamide-exposed female fathead minnows and zebrafish. Identification of genes and pathways impacted across fish species may support biomarker development for reproductive effects associated with antiandrogens.