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THE HERBICIDE LINURON REDUCES FETAL TESTOSTERONE PRODUCTION DURING BOTH IN UTERO AND IN VITRO EXPOSURES
Citation:
WILSON, V. S., C. R. LAMBRIGHT, J. FURR, K. HOWDESHELL, AND L. E. GRAY. THE HERBICIDE LINURON REDUCES FETAL TESTOSTERONE PRODUCTION DURING BOTH IN UTERO AND IN VITRO EXPOSURES. Presented at Society for the Study of Reproduction, QUEBEC CITY, QC, CANADA, July 24 - 27, 2005.
Description:
Linuron, a urea-based herbicide, is a weak antagonist for the androgen receptor. Previous studies in our lab have shown that in utero exposureresults in malformations of androgen dependent tissues in adult male offspring. The pattern of malformations, however, differs somewhat from that typically seen with a pure androgen receptor antagonist. The goal of the present study was to investigatethe impact of linuron treatment administered in utero during the critical period of sex differentiation upon testosterone production from the fetal testis. Timed-pregnant Sprague-Dawley rats were administered either corn oil vehicle or 12.5, 25, 50 or 75 mg/kg/day linuron by gavage from GD13-18 (n= 4-8 liters per dose group). On GD18, individual testes were removed and incubated to evaluate ex vivo testosterone (T) production. When analyzed on an individual fetus basis, ex vivo testosterone production was significantly decreased in a dose dependent manner at all treatment levels. However, on a per litter basis, testosterone was significantly reduced only at 50 and 75 mg/kg. To determine if linuron could directly inhibit testosterone production in the fetal testes, GD18 untreated fetal testes were incubated in vitro in medium with increasing concentrations of linuron (1, 3, 10, 30, 100, or 300 microM). In this experiment, testosterone production from fetal testes was significantly reduced at 30 microMand above indicating that linuron can directly inhibit testosterone production. Additional studies are planned to evaluate changes in gene expression of enzymes in the androgen synthesis pathway. Results to date would indicate that the malformations produced by linuron in male offspring are likely due, at least in part, to inhibition of fetal testosterone production during the critical period of sex differentiation during gestation. Disclaimer: Abstract does not necessarily reflect EPA policy.