Transplacental administration of diethylstilbestrol (DES) causes lesions in female reproductive organs of Donryu rats, including endometrial neoplasia

The effects of transplacental administration of diethylstilbestrol (DES) on female reproductive organs were investigated using Donryu rats. The animal s were given subcutaneous injections of DES dissolved in olive oil at doses of 0.01 or 0.1 mg/kg on days 17 and 19 of gestation. In female offspring, clinical signs, body weights and estrous cycles were continuously assessed until all survivors were killed at month 18, A low mean litter size and sho rtening of period of pregnancy were recognized in the 0.1 mg/kg group. Diso rder and/or suspension of the estrous cycle (so called persistent estrus) a lso appeared very early in the 0.1 mg/kg group. Macroscopically, the incide nces of hypoplasia of the oviduct, cystic dilatation of the uterus and smal l size of the uterine cervix were higher in the 0.1 mg/kg group than those in the control group. Histologically, in the ovary, the incidence and degre e of atrophy were increased in both 0.01 and 0.1 mg/kg groups. Ln the uteru s, total incidences of endometrial hyperplasias were about the same in all groups. However, endometrial adenocarcinomas were dose-dependently increase d in the treated soups, the incidence in the 0.1 mg/kg group being signific ant, compared to that in the control. In the vagina, mucification was more prominent in the treated animals, especially at the higher dose, but no tum ors were observed. The present results indicate that prenatal exposure to D ES can produce uterine adenocarcinomas in rats, as reported earlier for mic e, although its carcinogenic activity is not so strong. Increase of endomet rial adenocarcinoma incidence might depend on hormonal imbalance resulting from the ovarian atrophy due to transplacental treatment of DES. (C) 1999 E lsevier Science Ireland Ltd. All rights reserved.