Involvement of granule-mediated apoptosis in the cyclic changes of the normal human endometrium

Our objective is to investigate the involvement of granule-mediated apoptos is in the cyclic changes of the endometrium. We demonstrated the localizati on of CD56, perforin, granzyme B and caspase-3 in the endometrium by immuno histochemistry. We also confirmed the localization of perforin by immune-el ectron microscopy, and demonstrated apoptosis in endometrial glandular cell s by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and electron micros copy. Uterine CD56-positive natural killer (NK) cells expressed perforin an d granzyme B in its cytoplasm. Uterine NK cells increased significantly in the endometrial stroma during the secretory phase, and peaked during the la te secretory phase. These cells started decreasing in number during the men strual period. In endometrial glandular cells, caspase-3 and TUNEL-positive cells increased significantly from the late secretory phase, with apoptosi s reaching a peak during the menstrual period. Using electron microscopy, w e observed uterine NK cells with chromatin rich, segmented nuclei and intra cytoplasmic granules in the stroma obtained from late secretory phase endom etria. These cells extended projections to the lining of endometrial glandu lar cells and attached to form a cell-to-cell contact. In addition, nuclear chromatin was observed to have already cohered and small cytoplasmic organ elles were beginning to disappear, suggesting that these endometrial glandu lar cells were undergoing apoptosis. Utilizing immune-electron microscopy, intracytoplasmic granules in uterine NK cells were stained with anti-perfor in antibody. The findings of this study suggest that granule-mediated apopt osis in endometrial glandular cells induced by NK cells expressing perforin and granzyme B may be associated with the onset of menstruation. - apoptos is; endometrium; NK cell; perforin; granzyme B (C) 2001 Tohoku University M edical Press.