Apoptosis in the human uterine endometrium during the menstrual cycle.

To investigate apoptotic changes, we studied the cleavage of DNA in the uterine endometrium obtained from regularly cycling women by a quantitative end labeling of DNA gel fractionation and in situ analysis. The ladder pattern characteristic of the apoptotic cleavage of DNA into fragments of low mol wt was identified at three different phases of the cycle, namely the early proliferative, late secretory, and menstrual phases. However, DNA of high mol wt was predominant in the endometrium during the late proliferative, early secretory, and midsecretory phases. Our analysis in situ revealed that cells undergoing apoptosis were scattered in the functional layer of the early proliferative endometrium. However, apoptotic cells were no longer detectable during the late proliferative phase, and none was observed until the midsecretory phase. At the beginning of the late secretory phase, apoptosis reappeared in the stromal cells and spread gradually to almost all components of the functional layer. By contrast, cells in the basal layer showed no evidence of apoptosis throughout the menstrual cycle. The present study demonstrates that apoptosis occurs in specific populations of cells during three phases of the human endometrial cycle. Our results indicate, moreover, that apoptosis might have an important role in the regulation of the menstrual cycle in women.