Eli Maymon, Roberto Romero, Percy Pacora, Ricardo Gomez, Moshe Mazor, Sam Edwin, Tinnakorn Chaiworapongsa, Ju Cheol Kim, Bo Hyun Yoon, Ramkumar Menon, Stephen Fortunato, Stanley M. Berry
A role for the 72 kDa gelatinase (MMP-2) and its inhibitor (TIMP-2) in human parturition, premature rupture of membranes and intraamniotic infection
Objective: Degradation of the extracellular matrix in
fetal membranes has been implicated in the process of
parturition and rupture of membranes. Matrix metalloproteinases
(MMPs) are enzymes capable of degrading
extracellular matrix including collagen. Tissue inhibitors
of matrix metalloproteinases (TIMPs) inhibit the
activity of MMPs by covalently binding to the enzymes.
MMP-2 degrades Type IV collagen and TIMP-2 is its
specific inhibitor. The objective of this study was to
determine if human parturition, rupture of membranes
(term and preterm) and microbial invasion of the amniotic
cavity (MIAC) are associated with changes in the
concentrations of MMP-2 and TIMP-2 in amniotic
fluid.
Study design: A cross-sectional study was conducted
with women in the following categories: 1) term with
intact membranes, in labor and not in labor; 2) preterm
labor and intact membranes who delivered at term, who
delivered preterm and preterm labor with MIAC; 3) preterm
premature rupture of membranes (PROM) with
and without infection; 4) term and preterm PROM not
in labor; and 5) midtrimester. MMP-2 and TIMP-2 concentrations
in amniotic fluid were determined using sensitive
and specific immunoassays.
Results: The concentration of TIMP-2 increased with advancing
gestational age (r = 0.6, p < 0.001). No correlation
was found between MMP-2 concentrations and gestational
age. Human parturition and rupture of membranes
(term and preterm) and in patients with intact
membranes were not associated with changes in the amniotic
fluid MMP-2 concentrations. In contrast, 1) patients
with spontaneous labor (term and preterm) had significantly
lower median concentrations of TIMP-2 compared
to those not in labor (p < 0.05 for both); 2) MIAC
in women with preterm labor and preterm PROM was associated
with a significant decrease in amniotic fluid
TIMP-2 concentrations (p < 0.04 for both comparisons);
3) Rupture of the membranes (term and preterm)was also
associated with a significant decrease in the amniotic
fluid TIMP-2 concentrations (p < 0.05 and p < 0.03,
respectively).
Conclusions: Human parturition (preterm and term),
rupture of fetal membranes (term and preterm) and
intraamniotic infection are associated with a significant
decrease in amniotic fluid TIMP-2 concentrations.
Journal of Perinatal Medicine, Walter de Gruyter
Print ISSN: 1619-3997
Volume: 29, 08/2001
Pages: 308 - 316
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