Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection

OBJECTIVES: The mechanisms by which microbial invasion of the amniotic cavi ty leads to membrane weakening and rupture are poorly understood. Recently. endogenous host enzymes have been implicated in this process. Matrix metal loproteinases are a family of potent enzymes that degrade components of the extracellular matrix. Collagen type I provides the main tensile strength o f the fetal membranes. Matrix metalloproteinase 8 (MMP-8), or neutrophil co llagenase, degrades interstitial collagens, acting preferentially on collag en type I. This study was undertaken (1) to determine whether MMP-8 is pres ent in amniotic fluid and whether its concentrations are changed in preterm and term labor and membrane rupture with and without intra-amniotic infect ion and (2) to determine whether the amniotic fluid concentrations of MMP-8 in labor at term are different in the lower and upper uterine compartments . STUDY DESIGN: A cross-sectional study was conducted and transabdominal amni ocentesis was performed in women in the following categories: (1) midtrimes ter (n = 25), (2) preterm labor in the presence and absence of microbial in vasion of the amniotic cavity (n = 86), (3) preterm premature rupture of th e membranes in the presence and absence of microbial invasion of the amniot ic cavity (n = 51), (4) term patients in labor and not in labor (n = 51), a nd (5) term premature rupture of membranes (n = 20). Additional paired samp les of amniotic fluid were retrieved by transabdominal amniocentesis (upper compartment) and transvaginal amniocentesis (lower or forebag compartment) from 14 term patients (28 samples) in spontaneous labor with intact membra nes. Amniotic fluid MMP-8 concentrations were determined with a sensitive a nd specific immunoassay. RESULTS: MMP-8 was detected in 95.4% (249/261) of all samples. (1) Spontane ous human parturition was associated with a significant increase in amnioti c fluid concentrations of MMP-8 in both term and preterm gestation. Term (n o labor median, 3.3 ng/mL; range, <0.06-38.6 ng/mL; vs labor median, 16.6 n g/mL; range, 0.33-1650 ng/mL; P < .05). Patients with preterm labor who del ivered preterm (in the absence of microbial invasion of the amniotic cavity ) had a significantly higher median amniotic fluid MMP-8 concentration than those with preterm labor who delivered at term (preterm labor, term delive ry median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm labor, preterm d elivery median, 32.5 ng/mL; range. <0.06-6006.6 ng/mL; P < .003). (2) Spont aneous rupture of membranes in preterm gestation but not in term gestation was associated with elevated amniotic fluid concentrations of MMP-8. Preter m gestation (preterm labor, intact membranes median. 3.1 ng/mL; range, <0.0 6-415.1 ng/mL; vs preterm premature rupture of membranes median, 35.1 ng/mL ; range, 0.71-1184.1 ng/mL; P < .05). Term gestation (intact membranes medi an, 3.3 ng/mL; range, 0.24-38.6 ng/mL; vs rupture of membranes median, 5.6 ng/mL; range, 0.22-19.8 ng/mL; P = .9). (3) Microbial invasion of the amnio tic cavity was associated with a significant increase in amniotic fluid MMP -8 concentration in patients with preterm labor and intact membranes, as we ll as in patients with preterm premature rupture of membranes. Preterm labo r (no microbial invasion of the amniotic cavity, preterm delivery median, 3 2.5 ng/mL; range, <0.06-6006.6 ng/mL; vs microbial invasion of the amniotic cavity median, 208.1 ng/mL; range, 4.2-14,600 ng/mL; P < .001). Preterm pr emature rupture of membranes (no microbial invasion of the amniotic cavity median, 35.1 ng/mL; range, 0.71-1184.1 ng/mL; vs microbial invasion of the amniotic cavity median, 317.9 ng/mL; range, 2.16-14,500 ng/mL; P < .01). (4 ) The median amniotic fluid MMP-8 concentrations were significantly higher in fluid obtained from the forebag compartment than in that obtained from t he upper compartment (median, 66.2 ng/mL; range, 7.4-170 ng/mL; vs median, 13.3 ng/mL; range, 2-170 ng/mL; respectively; P < .01). CONCLUSIONS: These data suggest a role for a specific interstitial collagen ase (MMP-8) in microbial invasion of the amniotic cavity, preterm membrane rupture, and term and preterm labor. The higher concentration of MMP-8 in f luid bathing the cervical region may explain the predilection for membrane rupture to occur close to the lower pole of the uterus.