title: Reproductive toxicity of vinclozolin in the fathead minnow: confirming an anti-androgenic mode of action.
abstract: 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 17beta-trenbolone (TB). Effects on fecundity, gonadal histology, secondary sexual characteristics, reproductive hormones, and relative abundance of androgen receptor (AR) and 11beta-hydroxysteroid dehydrogenase (11betaHSD) 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 microg/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 betaHSD 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.
authors.affiliation: Mid-Continent Ecology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US EPA, Duluth, MN 55804, USA. martinovic.dalma@epa.gov
authors.forename: Dalma
authors.initials: D
authors.lastname: Martinović
authors.forename: Lindsey S
authors.initials: LS
authors.lastname: Blake
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Durhan
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Greene
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kahl
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Jensen
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Makynen
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
mesh_terms: D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000818:Animals; D003531:Cypriniformes / Q000097:blood / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010080:Oxazoles / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D014819:Vitellogenins / Q000097:blood / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D020533:Angiogenesis Inhibitors; D005659:Fungicides, Industrial; D010080:Oxazoles; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D013739:Testosterone; D004958:Estradiol; C025643:vinclozolin