Stephen J. Fortunato, Ramkumar Menon, Salvatore J. Lombardi
MMP/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture
Objective: We theorize that excessive degradation of
the fetal membrane extracellular matrix (ECM) by specific
matrix metalloproteinases (MMPs) results in preterm
premature rupture of the membranes (PROM).
Active, inhibitor free MMP2 and 9 (gelatinase A and B
respectively) can degrade the amniochorion basement
membrane Type IV collagen to initiate rupture. This
study examines the levels of the gelatinases and their natural inhibitors (tissue inhibitor of matrix metalloproteinases -TIMPs) in the amniotic fluid during PROM,
preterm labor (PTL) and at term.
Methods: A total of 51 AF samples were collected
from the following groups of patients. Group 1: Women with PTL and no ROM (n = 16) Group 2: Women with PROM (n = 16) irrespective of labor
status Group 3: Women at term with intact membranes undergoing cesarean delivery irrespective of
labor status (n = 19). ELISA was used to assay
MMP2, MMP9, TIMP1 and TIMP2 levels in the amniotic
fluid. The active, TIMP free levels of MMP2
were quantitated by zymography followed by computerized
densitometry. Active MMP9 was measured
using a bioassay that specifically detects MMP9 activity.
Statistical analysis was performed by Tukey-Kramer multiple comparison method.
Results: PROM is associated with increased MMP2
levels (mean 2125 ng/ml;) when compared with term
(mean 1455 ng/ml; p < 0.01) or PTL where a non
significant increase was seen (mean 1862 ng/ml;
p = ns). MMP9 levels were higher in PROM (mean
15.03 ng/ml) than at term (mean 1.14 ng/ml;
p < 0.001) or PTL (mean 3.75 ng/ml; p < 0.01).
TIMP1 levels were slightly increased during PROM (mean 3143 ng/ml) compared to term (mean 1892 ng/
ml; p < 0.05) pr PTL where a non significant change
was seen (mean 2406 ng/ml; p 5 ns). TIMP2 levels
were decreased in PROM (mean 98 ng/ml) compared
with term (mean 176 ng/ml; p < 0.05) and PTL (mean
236 ng/ml; p < 0.001). Active, TIMP free MMP2
levels were increased during PROM (mean 233 pg/ml) compared to those at term (mean 132 pg/ml;
p < 0.05) or PTL (mean 132 pg/ml; p < 0.05). Active
forms of MMP9 were seen only during PROM (mean
632 pg/ml).
Conclusion: Active, TIMP free forms of MMP2 and
9 are increased in the amniotic fluid of women with
PROM. These MMPs can degrade the amniochorion
basement membranes and other ECM components resulting
in PROM.
Journal of Perinatal Medicine, Walter de Gruyter
Print ISSN: 1619-3997
Volume: 27, 11/1999
Pages: 362 - 368
Show full article (external site)
Show all available items of this journal
Search
