Fetal programming of adult uterine response to estrogen [abstract]
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The objective of this study was to examine the effects of fetal exposure to estrogenic chemicals on the subsequent response of the uterus to estrogen in female mice. In adult mice, estrogen rapidly stimulates the intake of fluid into the uterus, sometimes doubling it in size. Pregnant CD-1 strain mice were dosed with varying amounts of diethylstilbestrol (DES), a man-made estrogenic drug, during gestation. When 3 months old, one female offspring from each litter was injected with corn oil (oil controls), and another was injected with estradiol. The uterus and gonadal fat were collected and weighed three hours later, and the uteri were stored for subsequent analysis. Our data show that fetal exposure to a high dose of DES resulted in the uterus showing no uterine response to the estradiol injection. Females exposed to the low dose of DES during fetal life showed a significant increase in uterine weight when injected with estradiol in comparison to females not exposed to DES during fetal life and administered estradiol. Our hypothesis is that these outcomes are because the mechanisms mediating rapid fluid uptake into the uterus in response to estradiol are sensitized by low doses of DES and desensitized by high doses of DES during fetal life. This prediction will be examined by determining whether genes involved in regulating this response are imprinted by DES during fetal life.