REPRODUCTIVE TOXICITY OF VINCLOZOLIN IN THE FATHEAD MINNOW: CONFIRMING AN ANTI-ANDROGENIC MODE OF ACTION

• Published in: Environmental toxicology and chemistry Vol. 27; no. 2; pp. 478 - 488
• Main Authors: Martinovic, D, Blake, L.S, Durhan, E.J, Greene, K.J, Kahl, M.D, Jensen, K.M, Makynen, E.A, Villeneuve, D.L, Ankley, G.T
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Periodicals, Inc 01.02.2008; Blackwell Publishing Ltd
• Subjects: Androgens; Angiogenesis Inhibitors - toxicity; animal reproduction; Animals; Anti-androgen; Cypriniformes - blood; Cypriniformes - physiology; dose response; Dose-Response Relationship, Drug; ecotoxicology; Endocrine disruption; enzyme activity; Estradiol - blood; Estradiol - metabolism; fecundity; Female; Females; Fish; Fungicides, Industrial - toxicity; gonads; Health hazards; hormone receptors; Male; Males; Ovary - drug effects; Ovary - metabolism; Oxazoles - toxicity; Pimephales promelas; pollutants; Reproduction; Reproduction - drug effects; Studies; Testis - drug effects; Testis - metabolism; testosterone; Testosterone - blood; Testosterone - metabolism; toxicity; Trout; Vinclozolin; Vitellogenins - blood; Vitellogenins - metabolism; Water Pollutants, Chemical - toxicity; water pollution
• ISSN: 0730-7268; 1552-8618
• DOI: 10.1897/07-206R.1

The objective of the present study was to characterize responses of the reproductive endocrine system of the fathead minnow (Pimephales promelas) to the fungicide vinclozolin (VZ), using a 21-d reproduction assay, and a shorter-term (approximately two weeks) test in which fish were cotreated with the VZ (a putative anti-androgen) and the androgen 17β-trenbolone (TB). Effects on fecundity, gonadal histology, secondary sexual characteristics, reproductive hormones, and relative abundance of androgen receptor (AR) and 11β-hydroxysteroid dehydrogenase (11βHSD) mRNA transcripts were evaluated in one or both of these studies. Fecundity of VZ-exposed fish was decreased in a concentration-dependent manner in the 21-d test, culminating in complete reproductive failure at a concentration of 700 μg/L. Exposure to VZ decreased expression of male secondary sexual characteristics--an effect typical of anti-androgens. The finding that exposure of females to TB-induced expression of prominent, male-like tubercles, which could be effectively blocked with VZ, provides powerful evidence of the anti-androgenic activity of VZ in vivo. In the two experiments VZ produced several responses possibly indicative of compensation or adaptation of the fish to the anti-androgen, including increases in gonad weight, AR and 11 βHSD mRNA transcript abundance, and ex vivo gonadal production of testosterone and 11-ketotestosterone. Overall, our results demonstrate that the model anti-androgen VZ, which also is an environmental contaminant, impairs reproductive success of fathead minnows and elicits endocrine responses consistent with an anti-androgenic mode of action.