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.
Mertens
Helena J M M
HJ
Department of Obstetrics and Gynecology, Research Institute Growth and Development, GROW, University Hospital Maastricht, The Netherlands. hmertens@orbisconcern.nl
Heineman
Maas J
MJ
Evers
Johannes L H
JL
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