INCREASED MATRIX METALLOPROTEINASE ACTIVITY AND REDUCED TISSUE INHIBITOR OF METALLOPROTEINASES-1 LEVELS IN AMNIOTIC FLUIDS FROM PREGNANCIESCOMPLICATED BY PREMATURE RUPTURE OF MEMBRANES

OBJECTIVES: It has been suggested that increased matrix metalloprotein ases activity promotes the weakening of the amniochorion during normal and premature rupture of membranes. This study was designed to determ ine whether levels of matrix metalloproteinases and the tissue inhibit or of metalloproteinases-l in amniotic fluid change in a pattern consi stent with this hypothesis. STUDY DESIGN: Gelatinolytic activity, meas ured by a soluble substrate assay and zymography, and the concentratio ns of tissue inhibitor of metalloproteinases-l were estimated in amnio tic fluid obtained from (1) normal early gestations, (2) normal term p regnancies with labor, (3) normal term pregnancies without labor and ( 4) pregnancies complicated by premature rupture of membranes. The 92 k d type IV collagenase (matrix metalloproteinase-9) was also detected i n amniotic fluid by Western blotting. RESULTS: Matrix metalloproteinas e activities were higher in amniotic fluid from normal term pregnancie s with labor and pregnancies complicated by premature rupture of membr anes than from early pregnancies and term gestations without labor. Th e amniotic fluid from term pregnancies with labor or pregnancies with premature rupture of membranes contained several gelatinases, as revea led by zymography. The major amniotic fluid gelatinolytic activity in premature rupture of membranes and term pregnancies with labor corresp onded to matrix metalloproteinase-9. Tissue inhibitor of metalloprotei nases-l concentrations were highest in early-pregnancy amniotic fluid, followed by term gestation with labor, term gestation without labor, and premature rupture of membranes. CONCLUSIONS: Normal labor and prem ature rupture of membranes are associated with increased levels of mat rix metalloproteinases, particularly matrix metalloproteinase-9 in amn iotic fluid. Premature rupture of membranes is associated with reduced levels of tissue inhibitor of metalloproteinases-l. The imbalance bet ween matrix metalloproteinases and tissue inhibitor of metalloproteina ses-l in amniotic fluid may reflect a disorder that promotes premature rupture of membranes.