INCREASED TUMORS BUT UNCOMPROMISED FERTILITY IN THE FEMALE DESCENDANTS OF MICE EXPOSED DEVELOPMENTALLY TO DIETHYLSTILBESTROL

Prenatal exposure to diethylstilbestrol (DES) has been associated with the subsequent development of reproductive tract abnormalities, inclu ding poor reproductive outcome and neoplasia, in experimental animals and humans. Experimental animal studies with chemical carcinogens have raised the possibility that adverse effects of DES may be transmitted to succeeding generations. To evaluate this possibility and to determ ine if there is a sensitive window of developmental exposure, outbred CD-I mice were treated with DES during three stages of development: gr oup I was treated on days 9-16 of gestation (2.5, 5 or 10 mu g/kg mate rnal body wt), the time of major organogenesis; group II was treated o nce on day 18 of gestation (1000 mu g/kg maternal body wt) just prior to birth; group III was treated on days 1-5 of neonatal life (0.002 mu g/pup/day), Female mice (F1) in each group were raised to sexual matu rity and bred to control males. As previously reported, fertility of t he F1 DES-exposed females was decreased in all groups. Female offsprin g (DES lineage or F2) from these matings were raised to maturity and h oused with control males for 20 weeks. The fertility of these DES line age female mice was not affected by DES exposure of their 'grandmother s'. DES lineage mice were killed at 17-19 and 22-24 months of age. An increased incidence of malignant reproductive tract tumors, including uterine adenocarcinoma, was seen in DES lineage mice but not in corres ponding controls; the range and prevalence of tumors increased with ag e. Because uterine adenocarcinomas were seen in all three DES groups, all developmental exposure periods were considered susceptible to the adverse effects of DES, These data suggest that the reduced fertility observed in the DES F1 female mice was not transmitted to their descen dants; however, increased susceptibility to tumor formation is apparen tly transmitted to subsequent generations.