Effects of the mammalian antiandrogen vinclozolin on development and reproduction of the fathead minnow (Pimephales promelas)
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Previous work with the chlorinated fungicide vinclozolin and its metabolites, 2-{[(3,5-dichlorophenyl)-carbamoyl]oxy}-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), indicated antiandrogenic properties expressed in vivo as abnormalities in sexual differentiation of male rats after maternal exposures. In this study, we attempted to determine whether vinclozolin might also exhibit antiandrogenic properties in a model fish species, the fathead minnow, Pimephales promelas. In one study, embryonic (<6 h old) fathead minnows were exposed for approximately 34 days to five toxicant concentrations, ranging from 90 to 1200 µg l(-1), delivered via a flow-through diluter. The embryos were periodically sampled to determine survival, growth and gross pathology, and then placed in clean water for 4-6 months to assess long-term effects on sexual differentiation and subsequent reproductive success. Except for slightly reduced growth after 34 days in the highest vinclozolin concentration, no adverse effects were noted with respect to any of these endpoints. In a second experiment, adult fathead minnows were exposed to vinclozolin concentrations of approximately 200 or 700 µg l(-1) for 21 days, following which, gonadal morphology was assessed and serum sex steroid concentrations determined. Tissue samples from the exposed adults were assayed for vinclozolin and its metabolites. There was a slight increase in the serum beta-estradiol concentration of the male fathead minnows exposed to 700 µg vinclozolin l(-1), and a marked reduction in gonadal condition of female fish from this treatment. The possibility that vinclozolin and its metabolites would bind to androgen receptors in the fathead minnow was investigated through competitive radioligand binding studies. Vinclozolin, M1 and M2 failed to compete for high-affinity, low-capacity testosterone binding sites in fathead minnow brain and ovary cytosolic fractions, suggesting that these chemicals might not act as antiandrogens in the fathead minnow. More experimentation is necessary to determine whether responses observed in vivo might be due to the effects of vinclozolin (or its metabolites) on some other aspect of endocrine function.
