Effects of Postpubertal Oestrogen Injections on Mitotic Activity of Vaginal and Uterine Epithelial Cells in Mice Treated Neonatally With Oestrogen

Abstract

Cell cycles of vaginal and uterine epithelial cells were studies using [3H]thymidine autoradiography in adult ovariectomized mice given oestrogen injections neonatally. The mice were in a 'persistent-oestrous' state, showing ovary-independent, continued proliferation and cornification of the vaginal epithelium. The duration of different stages of the cell cycle could not be assessed in such mice, since the percentage of labelled mitoses failed to rise to 100%. In neonatally oestrogenized, adult mice the vaginal epithelium appeared to contain a mixed population of cells. After an oestrogen injection, almost all mitoses of vaginal epithelial cells became labelled, with a generation time of about 17 h. By contrast, the generation time was about 15 h in vaginal epithelial cells of ovariectomized 'normal' mice injected with oestrogen when adult. The uterine epithelium of neonatally oestrogenized, ovariectomized mice also consisted of a mixed population of cells. A single oestrogen injection produced an increase in both the mitotic rate and cell number in the vaginal and uterine epithelium of ovariectomized 'normal' adults but not in neonatally oestrogenized, ovariectomized adults. These studies show that in mice given oestrogen neonatally, uterine and vaginal epithelial cells were not responsive to oestrogen or at least less sensitive to oestrogen than ovariectomized 'normal' controls.

Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: II. Effects of DES on development

“…PM, perimetrial surface;epi, epithelium. al., 1977;McLachlan et al, 1980;Gilloteaux et al, 1982;Maier et al, 1985;Forsberg et al, 1985;Ostrander et al, 1985;Iguchi and Takasugi, 1987) and a decreased responsiveness to the growth promoting effects of estrogen in adulthood (Mori, 1967(Mori, , 1975Takasugi et al, 1970;Lerner et al, 1977;Gellert et al, 1977;Aihara et al, 1980;Maier et al, 1985;Ostrander et al, 1985;Iguchi and Takasugi, 1987). Uterine hy- poplasia also observed in this study is likely to be the consequence of disturbances in uterine mesenchymal growth and differentiation, since the derivatives of uterine mesenchyme (endometrial stroma and myometrium) normally give rise to 90-95% of the uterine mass (Martin et al, 1973;McCormack and Glasser, 1980) and define the overall size and shape of the uterus (Konishi et al, 1984).…”

Ultrastructure of the uterine epithelium of mice treated neonatally with estrogen

“…Following combined injections of progesterone and 17/?-estradiol after ovariectomy, incidence of deciduomata in response to uterine trauma is definitely lowered in steroid-treated rats as compared with that in the non-treated control animals similarly treated [Takewaki and Ohta, 1974;Olua and Takewaki, 1976], To obtain the greatest effect of neonatal administration of estrogen on the uterine epithelium, the dose of estrogen and the time of autopsy in the present experiments were determined on the basis of previous findings [Mori, 1975], The apical surface of the uterine epithelial cells of ovariectomized mice under goes some marked changes in response to estrogen. When exposed to estrogen, micro villi increase in length and the surface takes a fuzzy appearance.…”

“…In mice treated with estrogen as neonates and ovariectomized as adults, a reduction in the uterine capacity to react to exogenous estrogen has been demonstrated by the studies on the uterine weight, mitotic rate and cell number in the uterine epithelium [Mori, 1967[Mori, , 1975Takasugi and Kimura, 1967]. Following combined injections of progesterone and 17/?-estradiol after ovariectomy, incidence of deciduomata in response to uterine trauma is definitely lowered in steroid-treated rats as compared with that in the non-treated control animals similarly treated [Takewaki and Ohta, 1974;Olua and Takewaki, 1976], To obtain the greatest effect of neonatal administration of estrogen on the uterine epithelium, the dose of estrogen and the time of autopsy in the present experiments were determined on the basis of previous findings [Mori, 1975], The apical surface of the uterine epithelial cells of ovariectomized mice under goes some marked changes in response to estrogen.…”

Effects of estrogen treatment on persistent hyperplastic lesions of the vagina in neonatally estrogenized mice.

“…One of the possible explanations of the ineffectiveness of secondary estrogen treatment relates to the changes in sensitivity to exogenous steroids. Mori (1969Mori ( , 1975 and Iguchi (1977) reported that in neonatally estrogenized or androgenized vaginae estrogen was less likely to increase mitotic activity. A reduction in sensitivity to estrogen was also demonstrated by comparing the amount of material stored in the lumina of the transplanted vagina (Takasugi and Kimura, 1967).…”