ELEVATED PROTEASE ACTIVITIES IN HUMAN AMNION AND CHORION CORRELATE WITH PRETERM PREMATURE RUPTURE OF MEMBRANES

OBJECTIVES: The mechanism(s) of preterm premature rupture of fetal mem branes resulting in preterm birth remains unknown. Studies suggest tha t fetal membranes are susceptible to weakening by protease attack and that collagenases may be active at the site of rupture. In this study fetal membranes from women delivered after preterm premature rupture o f membranes were compared with control membranes and analyzed qualitat ively and quantitatively for protease activities. STUDY DESIGN: Fourte en membranes from women with preterm premature rupture of membranes an d nine membranes from women delivered preterm without premature ruptur e of membranes or otherwise normal women delivered at term vaginally o r by cesarean section were studied. Zymogram gel electrophoresis with gelatin incorporation was used to assess the number and apparent molec ular weights of protease activities. Functional and quantitative studi es of protease activity were measured by fluorescent substrate cleavag e. RESULTS: Zymogram gel electrophoresis studies demonstrated the pres ence of five to seven different protease bands in preterm premature ru pture of membranes samples, whereas control membranes demonstrated onl y one to three protease bands. Fluorescent studies of protease activit y demonstrated a 10- to 40-fold increase in activity in membranes from women with preterm premature rupture of membranes compared with norma l control membranes. Studies with protease inhibitors suggest that mos t of the activity is due to metalloproteinases. CONCLUSION: In membran es from women with preterm premature rupture of membranes there appear s to be a general increase in the amount of protease activity and incr eased numbers of putatively different proteases. Increased activity or deregulated protease control may mediate preterm premature rupture of membranes and be a potentially remediable cause of preterm birth.