Evidence of in vivo differential bioavailability of the active forms of matrix metalloproteinases 9 and 2 in parturition, spontaneous rupture of membranes, and intra-amniotic infection

OBJECTIVE: Matrix metalloproteinases (MMP-9 and MMP-2) have been implicated in the digestion of fetal membranes. The purpose of this study was to dete rmine the amniotic fluid concentrations of active forms of MMP-2 and MMP-9 and to explore the participation of these enzymes in labor (term and preter m), rupture of membranes (term and preterm), and microbial invasion of the amniotic cavity. STUDY DESIGN: A cross-sectional study was conducted with 291 women in the f ollowing categories: (1) term not in labor, (2) term in labor, (3) preterm labor and intact membranes who delivered at term, (4) preterm labor who del ivered preterm, (5) preterm labor with microbial invasion of the amniotic c avity, (6) preterm premature rupture of membranes without microbial invasio n of the amniotic cavity, (7) preterm premature rupture of membranes with m icrobial invasion of the amniotic cavity, (8) term premature rupture of mem branes not in labor, and (9) mid trimester. Active forms of MMP-2 and MMP-9 were measured by a novel assay that uses a substrate developed by protein engineering. RESULTS: (1) MMP-2 and MMP-9 were detected in 88% and 96% of amniotic fluid samples, respectively (255/291 and 279/291). (2) The concentrations of act ive forms of MMP-2 and MMP-9 changed with advancing gestational age. (3) Sp ontaneous term parturition was associated with a significant increase in th e median concentration of the active forms of MMP-9 (P < .005) and a signif icant decrease in the median concentration of the active forms of MMP-2 (P < .003). (4) Preterm labor with intact membranes leading to preterm deliver y in the absence of infection was associated with a significant increase in the median concentration of the active forms of MMP-9 (P < .005) but not o f the active forms of MMP-2 (P = .2). (5) Rupture of membranes (either term or preterm) was associated with a significant increase in the concentratio n of the active forms of MMP-9 and with a significant decrease in the conce ntration of the active forms of MMP-2 (P < .005 for term and P < .03 and P < .003 for preterm, respectively). (6) Microbial invasion of the amniotic c avity in women with preterm premature rupture of membranes was also associa ted with a significant increase in the concentration of the active forms of MMP-9 (P < .03) and a decrease in the concentration of the active forms of MMP-2 (P < .05). (7) Microbial invasion of the amniotic cavity in patients with preterm labor was associated with a significant increase in the media n concentration of the active forms of MMP-9 (P < .005) but not of the acti ve forms of MMP-2 (P = .6). CONCLUSION: Spontaneous rupture of membranes (either term or preterm), part urition (either term or preterm), and microbial invasion of the amniotic ca vity were associated with significant increases in the amniotic fluid conce ntration of the active forms of MMP-9. In contrast, the concentration of th e active forms of MMP-2 either decreased or remained the same in these cond itions. Our observations provide evidence for a novel regulation of gelatin olytic activity in vivo.