The expression of apoptosis-related proteins Bcl-2 and Ki67 in endometrium of ovulatory menstrual cycles.
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).


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Research Institute Growth and Development, GROW, University Hospital Maastricht, The Netherlands. hmertens@orbisconcern.nl
Helena J M M
HJ
Mertens
Maas J
MJ
Heineman
Johannes L H
JL
Evers
D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D002455:Cell Division; D015331:Cohort Studies; D004717:Endometrium / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008597:Menstrual Cycle / Q000502:physiology*; D008875:Middle Aged; D010060:Ovulation; D011336:Probability; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012016:Reference Values; D012038:Regeneration / Q000502:physiology*; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D015415:Biomarkers; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2