Development of Vaginal Epithelium Showing Irreversible Proliferation and Cornification in Neonatally Estrogenized Mice: An Electron Microscope Study *

Abstract

Irreversible proliferation and cornification of the mouse vaginal epithelium were induced by 10 daily injections of 20 pg estradioLl7p starting on the day of birth. Development of the irreversible vaginal epithelium during the period of estrogen injections in early postnatal life was observed under light and electron microscopes, Small electron-dense cells (A-cells) in clusters were present in the columnar vaginal epithelium of newborn mice. A-cells were proliferated by 2 daily estrogen injections. At the sites of A-cell clumps, large electron-dense cells (B-cells) characterized by long winding cytoplasmic processes appeared in mice given 3 daily injections, forming nodules which then fused together to form a layer under the columnar epithelium after 4 daily injections. In mice given 7 daily injections, the primary epithelium was shed by the superficial cornification of the newly formed layer. The Bcell membrane bore fewer desmosomes than in !he basal and intermediary cells of the vaginal epithelium of ovariectomized 'normal' adult mice after 5 daily injections of 100 pg estradioL17P. Hyperplastic epithelial downgrowths in old ovariectomized mice given neonatal estrogen injections contained another type of cells with reduced density which formed much fewer processes and only a few desmosomes (C-cells).Five to ten daily injections of estrogen starting on the day of birth cause proliferation and cornification of the mouse vaginal epithelium, which persist without further administration of estrogen (TAKASUGI, 1963; KIMURA et al., 1967;MORI, 1967;KOHRMAN and GREENBERG, 1968; for review, see TAKASUGI et ul., 1970). These changes in the vaginal epithelium are irreversible, frequently resulting in cancerous or precancerous lesions in neonatally estrogenized mice of more than 6 months of age (DUNN and GREEN, 1963; TAKASUGI and BERN, 1964; KIMURA and NANDI, 1967; MORI, 1969).Recently, TAKASUCI (1 97 1) has demonstrated that clumps of small-sized cells

Development of the Vaginal Epithelium Showing Estrogen-Independent Proliferation and Cornification in Neonatally Androgenized Mice

“…Takasugi (1971) and Takasugi and Kamishima (1973) have demonstrated that small cells (A-cells) present in small clusters beneath of the epithelium, the lining the fornico-cervical region and the junction of the Miillerian and sinus parts of the vagina are proliferated following neonatal injections of estrogen and nodules of larger cells (B-cells) later appear in and around these A-cell clusters. The nodules eventually undergo a marked proliferation under the normal columnar epithelium, The present findings appear to indicate that the mechanism involved in the induction of estrogen-independent persistent vaginal changes by neonatal injections of androgen is different from that following the neonatal administration of estrogen.…”

“…By contrast, have demonstrated that 5a-dihydrotestosterone (non-aromatizable androgen) given neonatally is also capable of inducing estrogenindependent persistent vaginal cornification in mice. Early development of the vaginal epithelium undergoing irreversible proliferation and cornification has already been studied in detail in neonatally estrogenized mice (Takasugi, 1971;Takasugi and Kamishima, 1973;. The present studies were attempted to investigate changes taking place in the mouse vaginal epithelium during and after neonatal androgen treatment inducing estrogen-independent persistent alterations.…”

Electron-microscopic study on the development of permanently proliferated and cornified vaginal epithelium in mice treated neonatally with androgen

“…Ultrastructural changes in the vaginal epithelium of neonatally estrogenized mice have been reported by Takasugi and Kamishima [1973] and Cunha et al [1978], but no such changes have been reported in neonatally androgenized mice. The present experi ments, therefore, were designed to study ultrastructural changes occurring during the development of perma nently altered vaginal epithelium in neonatally androgenized mice.…”

Ultrastructure of the uterine epithelium of mice treated neonatally with estrogen

“…Widened inter cellular spaces between basal cells contained many intertwined cytoplasmic processes. These basal cells look like basal cells of the vaginal epithelium in neonatally estrogenized mice [Takasugi and Kamishima, 1973;Mori el al., 1974]. In the vaginal epithelium, cells of this type are capable of undergoing autono mous proliferation.…”