Apoptotic cell death during the estrous cycle in the rat uterus and vagina.
BACKGROUND: Rodent uterus and vagina show marked histological changes during the estrous cycle. Apoptotic cell death has been demonstrated in hamster and rat uterine epithelium during the estrous cycle by electron microscopy: numerous epithelial cells undergo apoptosis at estrus. We examined cell death and cell proliferation in rat uterus and vagina during estrous cycle. METHODS: To examine the rate of proliferation in uterine and vaginal cells at each estrous stage, the numbers of cells at metaphase were counted separately in epithelial and stromal cells. We identified the apoptotic cells in uterus and vagina at each estrous stage by using DNA fragmentation, in situ DNA 3'-end labeling, and electron microscopy. RESULTS: Mitotic rates in uterine luminal and glandular epithelial cells were low at metestrus and estrus, respectively. Intense fragmentation was found in the uterus at metestrus and in the vagina at proestrus and metestrus. In uterine luminal and glandular epithelial cells, apoptotic index showed peaks at metestrus and estrus, respectively. In vaginal epithelial cells, many apoptotic cells were encountered in the superficial layer at proestrus, which may contribute to keratinization. In the middle and basal layer of vaginal epithelial cells, apoptotic index was high at metestrus, when mitotic rate was low. Electron microscopy confirmed the results of the labeling studies. CONCLUSIONS: Apoptotic cell death was encountered in the uterus and vagina during estrous cycle in rats. There is an inverse correlation between cell death and cell proliferation in rat uterine and vaginal epithelial cells during the estrous cycle.