IPRODIONE DELAYS MALE RAT PUBERTAL DEVELOPMENT, REDUCES SERUM TESTOSTERONE, AND DECREASES EX VIVO TESTICULAR TESTOSTERONE PRODUCTION

Abstract

Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to procymidone and vinclozolin, which are both known to antagonize the androgen receptor (AR). Based upon a pilot study, we hypothesized that pubertal exposure to IPRO would delay male rat pubertal development and reduce testosterone production within the testis. Sprague-Dawley weanling rats were dosed by gavage with 0, 50, 100, or 200 mg/kg/day of IPRO from postnatal day (PND) 23 to 51/52. The progression of preputial separation (PPS) was measured starting at PND 37. Organ weights, serum hormones, and ex vivo testis production under stimulated (+human chorionic gonadotropin (hCG)) and unstimulated (−hCG) conditions were measured at necropsy. IPRO delayed PPS at 100 and 200 mg/kg/day and decreased androgen sensitive seminal vesicle and epididymides weights. Furthermore, IPRO increased adrenal and liver weights. Serum testosterone levels were decreased along with serum progesterone and 17alphahydroxyprogesterone whereas serum LH was unaffected. IPRO reduced ex vivo testis production of testosterone, progesterone, and 17alphahydroxyprogesterone. Taken together, these results suggest that IPRO affects steroidogenesis within the testis, not through disruption of LH signaling, but possibly through inhibition of CYP11A (P450scc), Steroidogenic Acute Regulatory protein (StAR), or at some other point in the steroidogenic pathway before CYP17. These data, along with the reported failure of IPRO to elicit an AR antagonism response, provide evidence that IPRO differs from the dicarboximides procymidone and vinclozolin in that the effects on male rat pubertal development results from an inhibition of steroidogenesis and not AR antagonism. CRB supported through USEPA/NCSU Cooperative Training Agreement. This abstract does not necessarily reflect US EPA policy. (poster)