K. H. Park, T. Chaiworapongsa, Y.M. Kim, J. Espinoza, J. Yoshimatsu, S. Edwin, R. Gomez, B.H. Yoon, R. Romero
Matrix metalloproteinase 3 in parturition, premature rupture of the
membranes, and microbial invasion of the amniotic cavity
Objective. Matrix metalloproteinases (MMPs) are a family
of zinc-dependent endopeptidases that are expressed in
many inflammatory conditions and contribute to connective
tissue breakdown. Stromelysin 1 [matrix metalloproteinase
3 (MMP-3)], a novel member of this family, is
produced in the context of infection and is able to activate
the latent forms of other MMPs. The purpose of this study
was to determine if parturition (either term or preterm),
premature rupture of the membranes (PROM), and microbial
invasion of the amniotic cavity are associated with
changes in amniotic fluid concentrations of MMP-3.
Study design. A cross-sectional study was conducted,
which included women who underwent transabdominal
amniocentesis (n = 365) in the following categories: (1)
mid-trimester with a subsequent normal pregnancy outcome
(n = 84) and a subsequent fetal loss (n = 10); (2)
preterm labor with intact membranes without microbial
invasion of the amniotic cavity who delivered at term
(n = 36), or prematurely (n = 50), and preterm labor with
microbial invasion of the amniotic cavity (n = 25); (3)
preterm PROM with (n = 25) and without (n = 26) microbial
invasion of the amniotic cavity; (4) term with intact
membranes in the absence of microbial invasion of the
amniotic cavity, in labor (n = 52) and not in labor (n = 31);
and (5) term with PROM in the absence of microbial invasion
of the amniotic cavity and not in labor (n = 26).
MMP-3 concentrations in amniotic fluid were measured
by a sensitive and specific immunoassay that was validated
for amniotic fluid. MMP-3 concentrations were normalized
using logarithmic transformation for statistical
analysis. Parametric statistics were used and a p value
<0.05 was considered statistically significant.
Results. (1) MMP-3 was detected in 99.5% (363/365) of
amniotic fluid samples, and its concentration did not
change with advancing gestational age. (2) Spontaneous
parturition at term and preterm was associated with a
significant increase in amniotic fluid MMP-3 concentrations
(p = 0.04 and p = 0.002, respectively). (3) Spontaneous
rupture of membranes in term and preterm gestations
was not associated with significant changes in
amniotic fluid MMP-3 concentrations. (4) Intra-amniotic
infection was associated with a significant increase in
amniotic fluid MMP-3 concentrations in both women
with preterm labor and intact membranes (p = 0.03), and
women with preterm PROM (p = 0.02). (5) Subsequent
fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations
of amniotic fluid MMP-3.
Conclusions. (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms
of human parturition and in the regulation of the
host response to intrauterine infection.
Journal of Perinatal Medicine, Walter de Gruyter
Print ISSN: 1619-3997
Volume: 31, 01/2003
Pages: 12 - 22
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