Postnatal vaginal nodules induced by prenatal diethylstilbestrol treatment correlate with later development of ovary-independent vaginal and uterine changes in mice

Pregnant ICR JCL mice were given 4 daily subcutaneous injections of 0.2–2000 μg diethylstilbestrol (DES) starting on day 15 of gestation. Offspring of mothers given DES were killed at 1–10 days of age and examined for nodules of enlarged polygonal cells under the epithelium of the Müllerian (upper) vagina. Some offspring were ovariectomised at 30 days and killed at 120 days. The nodules which appeared in the prenatally DES-exposed mice (2–2000 μg/day) at 3–7 days were not connected with the epithelium of the sinus vagina and reacted positively to an antibody to epidermal growth factor. Nodule formation may prove to be prodromic of later ovary-independent vaginal changes in the DES-exposed mice. Epithelial stratification (2–2000 μg/day) and downgrowths and/or pegs (20–2000 μg/day) occurred in vaginae of ovariectomized mice exposed prenatally to DES; however, adenosis-like lesions occurred only in the offspring of mothers given the highest prenatal injections of 2000 μg DES. Wolffian remnants and hypospadias (2–2000 μg/day) were also encountered in the DES-exposed mice. Ovary-independent stratification of the uterine epithelium (20–2000 μg/day) and disorganization of the circular musculature (2–2000 μg/day) were also observed in the DES-exposed mice. None of these changes was found in ovariectomised 0.2 μg DES-exposed and control mice.