Development of vaginal adenosis-like lesions and uterine epithelial stratification in mice exposed perinatally to diethylstilbestrol.

Abstract

Pregnant ICR/JCL mice were given either four daily subcutaneous injections of 20-2000 micrograms diethylstilbestrol (DES)/day or a 4-day intravenous infusion of 20-200 micrograms DES/day starting on Day 15 of gestation. Female mice were injected with 0.01-50 micrograms DES/day for 5 days starting on the day of birth. Females given oil injections during the neonatal period and offspring of mothers given injections of an infusion of respective vehicles alone served as controls when corresponding ages were attained. Incidence of adenosis-like lesions (ADL) in the vaginal epithelium and stratification of the uterine epithelium (UST) were determined in both offspring and neonatally exposed mice at 30 days of age. Injections of 0.1-50 micrograms DES/day during the neonatal period induced ADL in the fornical epithelium of vagina (36-70%), but not UST. A high incidence of ADL (80-88%) was found in the fornical and upper-vaginal epithelia in offspring of mothers given injections of 200-2000 micrograms DES/day, and UST was encountered in 38-70% of these mice. Offspring of mothers given an infusion of 20 micrograms DES/day had low incidences of ADL (11%) and UST (22%), whereas offspring of mothers infused with 200 micrograms DES/day exhibited high incidences of ADL (71%) and UST (86%). In offspring of mothers given injections of 2000 micrograms DES/day, ADL appeared in the fornical and upper-vaginal epithelial as early as 15 days of age. Thus, the present study revealed that ADL and UST occur at a high incidence in infantile mice exposed prenatally to high doses of DES. Previous studies failed to detect such effects perhaps due to the strain of mice, methods, duration, and/or dose of DES used.