A PROGRAM OF CELL-DEATH AND EXTRACELLULAR-MATRIX DEGRADATION IS ACTIVATED IN THE AMNION BEFORE THE ONSET OF LABOR

Fetal membranes usually rupture during the process of labor. Premature fetal membrane rupture occurs not infrequently and is associated with significant fetal and maternal morbidity, The mechanisms of normal an d pathologic fetal membrane rupture are not well understood, We have e xamined structural and biochemical changes in the rat amnion as labor approaches in order to characterize this process in normal pregnancy, Here we report that before the onset of active labor the amnion epithe lial cells undergo apoptotic cell death which encompasses degradation of 28S ribosomal subunit RNA and associated P proteins and fragmentati on of nuclear DNA. Concurrent with these cellular changes, the amnion type I collagen matrix is degraded with the accumulation of three-quar ter length type I collagen fragments in extraembryonic fluid, characte ristic of the cleavage of fibrillar collagen by interstitial collagena se. Western blot and immunohistochemical analyses confirmed that inter stitial collagenase protein appears in association with the loss of am nion type I collagen. We conclude that amnion epithelial cells undergo a process of programmed cell death associated with orchestrated extra cellular matrix degradation which begins before the onset of active la bor. Thus, fetal membrane rupture is likely to be the result of bioche mical changes as well as physical forces.