Prevention by vitamin A of the occurrence of permanent vaginal and uterine changes in ovariectomized adult mice treated neonatally with diethylstibestrol and its nullification in the presence of ovaries

Abstract

Permanent proliferation and cornification of the vaginal epithelium occurred in adult ovariectomized (OVX) mice which had received neonatal injections of 5 micrograms diethylstilbestrol (DES). Occurrence of the permanent epithelial proliferation was prevented by injections of 200 IU vitamin A acetate (VA) given simultaneously with neonatal DES-treatment in mice when OVX at 30 days of age, but not in those OVX at 270 days. For the suppression of the permanent vaginal changes, however, more than one month were required after DES plus VA-treatment. In DES plus VA-treated OVX (at 30 days) mice, the vaginal epithelium indicated a lower mitotic rate than in DES-treated OVX mice. Clear cells were found in the degenerating vaginal epithelium in 63% of DES plus VA-treated OVX mice, while in the proliferated epithelium, this type of cells appeared only in 10% of DES-treated OVX mice. In 40% of 180-day-old, DES-treated OVX (at 30 days) mice, permanent stratification took place in the uterine epithelium, while it was inhibited in the age-matched DES plus VA-treated OVX mice. However, the uterine change was not prevented in 310-day-old, DES plus VA-treated mice when OVX at 270 days. This findings suggests that the relatively long-term presence of ovaries nullifys the inhibitory effect by VA on the occurrence of permanent changes in the utero-vaginal epithelium induced by neonatal DES treatment.