PARENT SESSION
MINISYMPOSIUM II. PRENATAL ORIGINS OF REPRODUCTIVE DYSFUNCTION IN THE FEMALE

Monday, August 2, 2004
9:00 AM–10:30 AM
Buchanan A100
Chair: Douglas L. Foster (University of Michigan, Ann Arbor, MI)

(MS4) EARLY PROGRAMMING OF REPRODUCTIVE DYSFUNCTION: SISTERS INFLUENCING BROTHERS IN UTERO: A LITTER-BEARING MODEL.

vom Saal, Frederick¹, Richter, Catherine¹, Welshons, Wade², Timms, Barry³, ¹ University of Missouri-Columbia, Columbia, MO² University of Missouri-Columbia, Columbia, MO³ University of South Dakota School of Medicine, Vermillion, SD

ABSTRACT- Rodent male and female fetuses differ in their serum levels of testosterone and estradiol based on whether they develop between two male or two female fetuses (the intrauterine position phenomenon). These relatively small differences in fetal steroids lead to significant differences in a wide variety of reproductive traits. While some phenotypic differences are mediated by differential fetal exposure to testosterone, experimental studies have shown that very small changes in serum estradiol also lead to marked changes in development of the male reproductive system. This raised the possibility that environmental chemicals and drugs with estrogenic activity might also alter development. To test this hypothesis we fed pregnant CD-1 mice on gestation day 14-18 a 0.1 micro g/kg/day dose of the estrogenic drug diethylstilbestrol (DES) as a positive control, a 0.1 micro g/kg/day dose of ethinyestradiol (5-fold lower than the dose in most oral contraceptives) or a 10 micro g/kg/day dose of bisphenol A, the estrogenic monomer used to manufacture polycarbonate plastic (this dose results in lower blood levels of bisphenol A in fetal mice than average levels in human fetuses). When examined on GD 19, we found that relative to negative controls, each of these estrogenic chemicals significantly increased the number and size of primary ducts in the dorsolateral prostate and induced a marked increase in proliferation of epithelial cells in the proximal region of the primary prostatic ducts, which preliminary evidence suggests are basal cells. There were also malformations in the urethra that could interfere with the regulation of urine flow. It is possible that acceleration of the rate of proliferation of prostate epithelium during fetal life by small amounts of estrogenic chemicals could permanently disrupt cellular control systems and predispose the prostate to disease in adulthood.

KEY WORDS: prostate, environmental estrogens, intrauterine position, urethra