Effects of Neonatal Diethylstilbestrol (DES) Exposure on Morphology and Growth Patterns of Endometrial Epithelial Cells in CD-1 Mice

Abstract

The effects of neonatal diethylstilbestrol (DES) exposure on the morphology and proliferating patterns of endometrial epithelial cells were investigated at various stages of development in mice. Female CD-1 mice were given daily subcutaneous injections of 2 μg of DES in corn oil or corn oil alone (control) at 1-5 days of age and were killed at 5, 6, 7, 8, 15, and 22 days of age. At 5 days of age, the uteri of DES-treated mice had expanded lumina and undulated luminal surfaces lined by slightly elongated epithelial cells. At 6-8 days of age, marked infolding of clusters of hypertrophic elongated luminal epithelial cells was present; uteri had disorganized endometrial stromal and myometrial layers. At 15 and 22 days of age, the tissues from DES-treated mice had decreased numbers of endometrial glands, minimal stromal fibrosis, and smaller uterine horns than did the controls. Ultrastructurally, the endometrial epithelial cells of DES-treated mice at 5 and 8 days of age had distorted nuclei with condensed matrix and abundant secretory granules associated with rough endoplasmic reticulum and Golgi apparatus. At 8 days of age, an accumulation of fingerlike cytoplasmic processes that extended into the separated intercellular spaces and along the basal aspects of the endometrial epithelial cells were also observed. At 5-8 days of age, the proliferative activity of endometrial epithelial cells in DES-treated mice, identified by bromodeoxyuridine labeling, was significantly lower (10.5-1.7%) than that of the controls (25.5-19.8%). In situ analysis of endometrial luminal epithelial cells for DNA fragmentation representing apoptosis revealed ≤0.1% and > 10% in the DES-treated and control mice at 5-8 days of age, respectively. The data show that cell cycle kinetics, in addition to changes in morphology, are altered in the developing mouse uterus following neonatal exposure to DES.