Reduced fertility in female mice exposed transplacentally to diethylstilbestrol (DES)

Prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, has been associated with a low incidence of vaginal adenocarcinoma as well as a variety of more numerous benign abnormalities in the reproductive tract of human beings and experimental animals. For the purpose of assessing the effects of prenatal exposure to DES on postnatal reproduction tract function, timed pregnant CD-1 mice were treated subcutaneously with doses of DES ranging from 0.01 to 100 microgram/kg/day on days 9 through 16 gestation. The fertility of the female offspring was determined postnatally by a repetitive forced breeding technique. The most striking effect observed was a dose-related decrease in reproductive capacity ranging from minimal subfertility at the lower DES doses to a high frequency of total sterility at the highest DES doses. Reduced reproductive capacity appeared to be a reflection of both a decrease in the total number of litters and smaller litter sizes. A major component of the sterility seen in those females given higher doses of DES was oviductal/ovarian, since the number of ova recovered from the oviductal ampullae after induced ovulation was less than 30% that of controls. In addition, structural abnormalities of the oviduct, uterus, cervix, and vagina were observed, and contributed to infertility. These data suggest that in utero exposure to DES results in permanent impairment of female mouse reproductive capacity. Recent reports of altered pregnancy outcomes in young women who were exposed in utero to DES demonstrate the clinical importance of the findings obtained in mice.