Morphological and Functional Consequences of Prenatal Exposure to Diethylstilbestrol in the Rat

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Abstract
Pregnant rats were treated with diethylstilbestrol (DES) during the second or third trimester of pregnancy to determine the effects of exposure to DES in utero on the offspring. Doses of DES in excess of 120 µg prevented parturition and resulted in the development of prominent nipples in both the male and female fetuses at term. The highest dose of DES which did not interfere with pregnancy and parturition in a majority of the pregnant animals was found to be 120 µg in the third trimester and 1.2 µg in the second trimester. Female offspring exposed to DES during the third trimester displayed precocious development of the nipples and opening of the vagina. Microscopically, nipple morphology was abnormal at the higher doses. At maturity, substantial numbers of animals exposed to 120 µg DES were found to have abnormalities of the external genitalia and reproductive organs, especially the ovaries. These structural abnormalities of the nipples and reproductive tracts are likely to account for the impaired fertility seen when these females were mated to untreated males and for their reduced capacity to support pups to weaning. While abnormalities of the external genitalia were noted in some animals exposed to 1.2 µg DES in the third trimester, these animals were normal with respect to fertility and morphology of the reproductive organs. Exposure to 1.2 µg DES during the second trimester was not associated with morphological abnormalities in the female offspring as neonates or adults or impairment of the fertility of these animals. Male sibs from all experimental groups did not appear structurally or functionally affected. These data demonstrate that the rat is a useful model system to study the effects of estrogenic hormones on a variety of fetal tissues.