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ANALYSIS OF ANDROGEN- AND EGF-RECEPTOR EXPRESSION IN THE FETAL RAT PHALLUS AFTER EXPOSURE TO VINCLOZOLIN
Citation:
Wolf, C J., B D. Abbott, G. A. LeBlanc, AND L E. Gray Jr. ANALYSIS OF ANDROGEN- AND EGF-RECEPTOR EXPRESSION IN THE FETAL RAT PHALLUS AFTER EXPOSURE TO VINCLOZOLIN. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
Analysis of Androgen- and EGF-Receptor Expression in the Fetal Rat Phallus After Exposure to Vinclozolin
Cynthia Wolf1,2, Barbara Abbott1, Gerald A. LeBlanc2, and L. Earl Gray, Jr.1
1USEPA, ORD, NHEERL, RTD, RTP, NC 27711, 2NCSU, Environmental and Molecular Toxicology, Raleigh, NC, 27695
Improper development of the male phallus during fetal sexual differentiation resulting in hypospadias is at least partially due to impaired androgen receptor (AR) function. Other mediators may be involved since hypospadias in humans is not usually associated with mutations of the AR. Epidermal growth factor (EGF) is suspected since it has been implicated in other developmental processes in the reproductive tract as an AR-dependent gene. The fungicide vinclozolin (V) is an AR inhibitor that induces cleft phallus and hypospadias in male rats exposed during fetal sexual differentiation. We investigated the ability of V to alter the expression of AR and EGF receptor (EGFR) in the fetal phallus at a dose that induces cleft phallus in the 100% of male offspring. Pregnant rats were dosed (po) with either corn oil (2.5 ml/kg) or V (400 mg/kg) on gestational days (GD) 14-18. On GD 18 phalluses were collected (3 phalluses/ 3 litters/ 3 treatment groups: control female, control male and V-treated male), fixed in 3% paraformaldehyde, dehydrated in ethanol and paraffin embedded. 6 m sections were placed on slides in matrix fashion with 1 representative per litter per treatment group per slide. Immunohistochemistry for AR or EGFR was performed by the avidin-biotin-peroxidase technique. Densitometric analysis of sections was performed blind using ImagePro Plus software. Mean density and area of the epithelial layers of the epidermis and the urethral groove, and number and summed area of receptor-positive cells in the mesenchyme was measured. We found a slight reduction in both AR and EGFR expression in control females as compared to control males, but no change in AR or EGFR expression by V. These results imply that events other than AR number or EGFR number mediate V-induced hypospadias. Future studies will focus on differences in gene expression induced by V that contribute to hypospadias. This abstract does not necessarily reflect EPA policy.