PARENT SESSION
PLATFORM SESSION 14: REPRODUCTIVE TOXICOLOGY AND ENDOCRINE DISRUPTION
Chair: Hoyer, Patricia¹, ¹
Co-chair: Benedict, Jamie¹, ¹
Dover A-C
2:00 PM-4:00 PM

(254) IN UTERO EXPOSURE TO DI(2-ETHYLHEXYL) PHTHALATE ALTERS GROWTH, TISSUE ORGANIZATION, AND THE EXPRESSION OF ANDROGEN RECEPTOR PROTEIN OF RAT PROSTATE.

Banerjee, Subhadra¹, Thuillier, Raphael¹, Culty, Martine¹, Papadopoulos, Vassilios¹, Brown, Terry², Banerjee, Partha¹, ¹ Dept. Cell Biology, Washington, DC² Dept. Biochemistry & Molecular Biology, Baltimore, MD.

ABSTRACT- Phthalate esters are postulated to have antiandrogenic properties. However, little is known regarding the impact of environmentally relevant exposure and biologically active concentrations of DEHP on the development of the prostate and seminal vesicles. DEHP was administered daily (93.5, 187, 280, 375, 500 and 750 mg/kg bw/day) by gavage to pregnant Sprague-Dawley dams from gestation day 14 to day of birth. The dose-related effects of DEHP on the ventral, dorsal, lateral and anterior lobe of the prostate and seminal vesicles of male offspring were determined at postnatal day 60. At the lowest dose of DEHP (93.5 mg/kg bw/day), tissue weight and DNA content of the ventral lobe increased by 1.2- and 1.5-fold, respectively. The other prostate lobes and seminal vesicles were unaffected at this concentration. By contrast, increasing amounts of DEHP (187, 280, 375, 500 and 750 mg/kg bw/day) caused a dose-dependent reduction in tissue weight in all prostate lobes and seminal vesicles. Treatment with lower doses of DEHP (93.5, 187, 280, 375 mg/kg bw/day) resulted in ventral lobe hyperplasia and dysplasia of epithelial cells with cribriform projections, similar to that seen in precancerous lesions. The number of PCNA-positive epithelial cells was increased by 2.5- to 3.5-fold in these lesions. Higher concentrations of DEHP (500 and 750 mg/kg bw/day) caused atrophy of the epithelium and significant lymphocytic infiltration in the ventral lobe within and surrounding the prostatic ducts. Androgen receptor expression appeared to be unchanged at lower doses (93.5 and 187 mg/kg bw/day) of DEHP, but progressively decreased with higher doses (280 and 370 mg/kg bw/day) and was absent at the highest doses (500 and 750 mg/kg bw/day) used. Interestingly, the highest doses of DEHP (500 and 750 mg/kg bw/day) caused partial or complete agenesis of the dorsal, lateral and anterior prostate lobes and seminal vesicles. These data indicate that environmentally relevant concentrations of DEHP administered during fetal life might alter the rat ventral prostate tissue organization and growth.

KEY WORDS: Phthalate, DEHP, Prostate, Androgen receptor