Estrogen changes mitosis orientation in the uterine epithelia

Abstract

Objectives: Estrogens can lead to hyperplasia and cancer formation in the uterus, ovary and mammary gland. However, key factors involved in this process are not defined at present. It is possible that estrogens primarily affect more global tissue-organising parameters as composition of tissues in three-metric space, that is brought about changes in the orientation of the plane of cell division. There are no data about estrogen action on mitosis orientation in the uterus. Study Design: Mitosis orientation, proliferative activity and general histology were examined in the uterus, jejunal and colonic crypts, and epidermis of ovariectomized rats 0, 24, 36 and 48 h after a single injection of estradiol, and in the uterus of ovariectomized mice received injections with estradiol once-a-week for 30, 60 and 90 days. Results: All mitoses in luminal and glandular epithelia of the uterus of ovariectomized rats aligned parallel to the basement membrane, and estradiol treatment leads to appearing of mitoses oriented perpendicular to the basement membrane of the epithelium. Together with increase in the proliferative activity, the number of perpendicular oriented mitoses in uterine epithelia of ovariectomized rats is significantly increased after a single injection of estradiol. During endometrial hyperplasia formation in mice, that is induced by chronic estrogen treatment, the number of perpendicular oriented mitoses in uterine epithelia become much more higher. In jejunal and colonic crypts, epidermis of ovariectomized rats, most of mitoses disposed parallel to the basement membrane and an injection of estradiol did not affect mitosis orientation and activity of proliferation. Conclusions: Estradiol effect on mitosis orientation may be considered as specific. Changes in mitosis orientation are probably responsible for estrogen-dependent hyperplasia and cancer formation in the uterus.