Apoptosis of human endometrium mediated by perforin and granzyme B of NK cells and cytotoxic T lymphocytes

Endometrial stromal granulocytes (EGs) were found to be a major component o f human endometrial stroma in the late secretory phase. However, the role o f EGs in the mechanism of human endometrial menstruation has not been clari fied. Immunohistochemistry of CD56, perforin, granzyme B, and vimentin, in situ detection of apoptosis by TUNEL (TdT-mediated dUTP-biotin nick and lab eling) and electron microscopy were performed in endometrial tissue samples with normal menstrual cycles. We analyzed the number of immunostained cell s in the functional layer of stroma and the number of apoptotic cells detec ted by TUNEL in the endometrial glandular cells. Double-staining revealed t hat CD56-positive endometrial stromal cells were simultaneously positive fo r both perforin and granzyme B, and negative for vimentin, which recognized stromal tissue. Vimentin was positive for the predecidual cells and negati ve for EGs. CD56-positive EGs involving perforin and granzyme B were progre ssively recruited during the secretory phases before menstruation. Apoptosi s in endometrial glandular cells increased from the late secretory phase, w hich maximized at the menstrual period. This finding suggests that the cyto toxic granules released from EGs, which are derived from cytotoxic T lympho cytes and natural killer cells, are initiators of the apoptotic pathway tha t induces endometrial menstruation.