DISTINCT REGIONAL AND MENSTRUAL-CYCLE DEPENDENT DISTRIBUTION OF APOPTOSIS IN HUMAN ENDOMETRIUM - POTENTIAL REGULATORY ROLE OF T-CELLS AND TNF-ALPHA

Human endometrium undergoes sequential cycles of proliferation, secret ion and menstrual shedding. Apoptosis constitutes a prominent feature of the menstrual process. In this study, we examined the regional and temporal distribution of the morphologically distinct apoptotic cells in human endometrium. Apoptosis was absent in the proliferative phase. It was first noted in the early secretory phase as individual or aggr egates of cells in subepithelial locations of endometrial glands. The rate of apoptosis progressively increased in the mid to late secretory phases and peaked in the menstrual phase. Apoptosis was rarely observ ed in the stroma. The identity of the apoptotic cells was further conf irmed by in situ demonstration of fragmented nuclear DNA. In addition, some of the apoptotic cells stained positively for cytokeratin favori ng their epithelial lineage. Apoptotic cells were preferentially distr ibuted in the basalis as compared to the functionalis glands. In addit ion, these cells were commonly found in association with intraglandula r or stromal lymphoid cells. Incubation of endometrial epithelial cell s with T cells and with TNF-alpha induced apoptosis and concomitantly inhibited proliferation of the epithelial cells in a dose dependent ma nner. In order to provide further evidence for the role of TNF-alpha i n the menstrual process, TNF-alpha was measured in the menstrual disch arge. As compared with the serum samples from the same patients, signi ficant TNF-alpha immunoreactivity was identified in the menstrual disc harge by ELISA. The findings show that apoptosis in endometrium is a m enstrual cycle dependent process that preferentially involves glandula r cells in the basalis. In addition, T cells and TNF-alpha may be the essential component of the mechanisms that lead to apoptosis in human endometrium and participate to the induction of menstruation.