The Expression of Apoptosis-Related Proteins Bcl-2 and Ki67 in Endometrium of Ovulatory Menstrual Cycles

Abstract

Background: During the menstrual cycle, a rapid sequence of proliferation, differentiation and cell death occurs in the human endometrium. Mechanisms involved in cell proliferation have been studied extensively. Apoptosis has recently been recognized to be a physiologic phenomenon. The aim of this study was to investigate the mechanisms involved in hormone-dependent tissue remodeling by measuring Bcl-2, an apoptosis inhibitor, and Ki67, a proliferation marker, as expressed in normal human endometrium. Methods: Paraffin-embedded endometrial sections of 30 uteri were immunostained for Bcl-2 and Ki67; expression was scored in cavitary epithelium, functional and basal glandular epithelial and stromal cells of the endometrium. Results: Bcl-2 expression increased in the proliferative phases and decreased significantly in the secretory phases, especially in glandular epithelial cells (131 ± 45 for functional laminal cells and 227 ± 68 for basal laminal cells to 0). Ki67 expression showed the same cyclic pattern with a later onset (145 ± 63 for functional laminal cells and 13 ± 8 for basal laminal cells to 0). Conclusion: Bcl-2 promotes cell survival by preventing apoptosis. Proliferation is the result of increasing estradiol concentration, high estrogen receptor expression and growth hormones and high Bcl-2 and Ki67 expression. After the onset of progesterone production, Bcl-2 levels decrease and Ki67 levels and androgen receptor expression in stromal cells disappear resulting in cell disintegration and menstruation. Persistent Bcl-2 expression, like we saw in basal laminal stromal and epithelial cells, accounts for the privilege of escaping from apoptosis-inducing signals. This allows reconstruction of the functional endometrium from its preserved basal layer after menstruation.