Journal Article

Propiconazole Inhibits Steroidogenesis and Reproduction in the Fathead Minnow (<i>Pimephales promelas</i>)

Sarah Y. Skolness, Chad A. Blanksma, Jenna E. Cavallin, Jessica J. Churchill, Elizabeth J. Durhan, Kathleen M. Jensen, Rodney D. Johnson, Michael D. Kahl, Elizabeth A. Makynen, Daniel L. Villeneuve and Gerald T. Ankley

in Toxicological Sciences

Volume 132, issue 2, pages 284-297
Published in print April 2013 | ISSN: 1096-6080
Published online January 2013 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kft010
Propiconazole Inhibits Steroidogenesis and Reproduction in the Fathead Minnow (Pimephales promelas)

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Conazoles are designed to inhibit cytochrome P450 (CYP) 14α-demethylase, an enzyme key to fungal cell wall formation. In vertebrates, conazoles may inhibit other CYPs, potentially disrupting processes like sex steroid synthesis. Propiconazole is a current-use pesticide that is among the first chemicals being tested in the U.S. Environmental Protection Agency endocrine disruptor screening program. Fathead minnows (Pimephales promelas) were exposed to 0, 5, 50, 500, or 1000 µg propiconazole/l in a 21-day study that evaluated apical reproductive endpoints (fecundity, fertility, hatch); measures of endocrine function and steroid synthesis, such as cholesterol, vitellogenin (VTG), and sex steroid (testosterone [T], 17β-estradiol [E2]) concentrations in the plasma; and changes in gonadal expression of steroidogenic genes. Plasma E2 and VTG concentrations in females were reduced by exposure to propiconazole, and egg production was decreased in the 500 and 1000 µg/l treatment groups. These in vivo effects coincided with inhibition of E2 synthesis by ovary explants exposed to propiconazole in vitro. We also observed a compensatory response in females exposed to propiconazole, manifested as increased gonad weight and upregulation of genes coding for key steriodogenic proteins, including CYP19 (aromatase), CYP17 (hydroxylase/lyase), CYP11A (cholesterol side-chain-cleavage), and steroidogenic acute regulatory protein. Other than an increase in relative testis weight, effects on endocrine function in males were less pronounced than in females. This study provides important data relative to the potential endocrine activity of propiconazole in fish and, more generally, to the further delineation of pathways for the reproductive effects of steroid synthesis inhibitors in fish.

Keywords: propiconazole; fish; reproduction; steriodogenesis; endocrine disruption.

Journal Article.  8897 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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