Related Experiment Video
Updated: Aug 8, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
MMP/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture
S J Fortunato1, R Menon, S J Lombardi
1Perinatal Research Center, Women's Health Research and Education Foundation, Nashville, TN, USA. fortunat@edge.net
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 = 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.
Insights
Elevated levels of active matrix metalloproteinases (MMPs), specifically MMP2 and MMP9, in amniotic fluid are linked to preterm premature rupture of the membranes (PROM). These enzymes degrade fetal membranes, initiating rupture.
Area of Science:
- Reproductive Biology
- Biochemistry
Background:
- Preterm premature rupture of the membranes (PROM) is a significant obstetric complication.
- Excessive degradation of the fetal membrane extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is theorized to cause PROM.
- Active, inhibitor-free MMP2 and MMP9 can degrade the amniochorion basement membrane, initiating rupture.
Purpose of the Study:
- To investigate the levels of MMP2, MMP9, and their inhibitors (TIMPs) in amniotic fluid from patients with PROM, preterm labor (PTL), and term pregnancies.
- To determine if active, TIMP-free MMP levels are associated with PROM.
Main Methods:
- Amniotic fluid samples were collected from 51 patients across three groups: PTL (n=16), PROM (n=16), and term controls (n=19).
- ELISA was used to quantify MMP2, MMP9, TIMP1, and TIMP2 levels.
- Zymography and a specific bioassay were employed to measure active, TIMP-free MMP2 and active MMP9, respectively.
Main Results:
- MMP2 and MMP9 levels were significantly higher in PROM cases compared to term controls.
- Active, TIMP-free MMP2 levels were elevated in PROM.
- Active MMP9 was detected exclusively in PROM cases.
- TIMP2 levels were decreased in PROM compared to both term and PTL groups.
Conclusions:
- Active, TIMP-free MMP2 and MMP9 are increased in the amniotic fluid of women experiencing PROM.
- These elevated MMPs likely contribute to the degradation of fetal membrane ECM, leading to PROM.
More Related Videos
08:50A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
06:32A Thermoplasmonic Approach for Investigating Plasma Membrane Repair in Living Cells and Model Membranes
Published on: January 19, 2024
Related Concept Videos
01:15Mechanisms of Membrane-bending
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
01:19Membrane Asymmetry Regulating Transporters
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
01:28Types of Membrane Protrusions
The microvilli, an example of stable protrusions, are finger-like projections with a...
01:23Role of Matrix Metalloproteases in Degradation of ECM
A...
01:17Intracellular Signaling Affects Focal Adhesions
Some...