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Effects of Neonatal Diethylstilbestrol (DES) Exposure on Morphology and Growth Patterns of Endometrial Epithelial Cells in CD-1 Mice
Akiyoshi Yoshida
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Retha R. Newbold
Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Darlene Dixon
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, MD C2-09, Research Triangle Park, North Carolina 27709, dixon{at}niehs.nih.gov.
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.
Key Words: Neonatal mouse • uterus • ultrastructure • immunohistochemistry • bromodeoxyuridine • apoptosis • endocrine disrupters • environmental estrogens
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Toxicologic Pathology, Vol. 27, No. 3,
325-333 (1999)
DOI: 10.1177/019262339902700308
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