Relation Of Matrix Metalloproteinases And Its Tissue Inhibitors And Premature Rupture Of The Fetal Membranes

Objective: Premature rupture of the fetal membranes(PROM)is a major complication of pregnancy associated with over 40﹪ of preterm labor. The pathophysiologic mechanisms underlying PROM was poorly understood. Extensive extra-cellular matrix(ECM)remodeling is found in many process during human parturition at term and preterm. These include cervical ripening, fetal membrane rupture, and placental detachment from the maternal uterus. Matrix metalloproteinases(MMPs)are the main mediaors of ECM degradation. Fetal membrane ECM comprising the basement membrane and the underlying stroma connects amnion and chorion cells together. Degradation of ECM by excessive MMPs activity has been described as the cause of rupture. Now MMPs and its TIMPs (tissue inhibitor of metalloproteinase) become the issue to study PROM. To identify MMP-2, 9 and TIMP-1, 2 in the mechanism of generation and development of PROM, and relationship between MMPs and its TIMPs in PROM, we investigate the expression of MMP-2, 9 and TIMP-1, 2 in the fetal membrane.Methods:(1) fetal membrane samples from patients at term who met entry criteria were selected. The study include women in the following categories: Control group(n=30)consisted of women not in labor with intact membranes (n=10) and women who delivered at term with intact membranes. PROM group(n=40)consisted of women with premature rupture of the membranes (PROM) not in labor (n=20) and women with PROM who delivered at term(n=20). PROM was defined as spontaneous amniorrhexis prior to the onset of labor. Membrane rupture was diagnosed using positive identifiers such as nitrazine test (fern test) pooling and oligohydramnios on ultrasound examination in the presence of the above. Group 4(n=20) consisted of women with PROM who delivered at term. (2) The expression of MMP-2, 9 and TIMP-1, 2 was studied by Flow Cytometry and Immunfluorescence. We took TIMP-1, 2 protein quantitative expression. Results:(1) Expression of MMP-2,TIMP-2 and ratio of MMP-2/TIMP-2 in different fetal membrane tissue: In Control group, the median MMP-2 Fetal membrane concentration was significantly higher in women who delivered at term than in women at term not in labor (term no labor, 1.0±0.04, vs term delivery, 1.30±0.05,p<0.01), but there was no difference in median TIMP-2 fetal membrane concentrations between women at term delivery and those at term not in labor(term no labor,1.00±0.04, vs term delivery, 1.00±0.04,p>0.05).ratio of MMP-2/TIMP-2 in fetal membrane was significantly higher in women who delivered at term than in women at term not in labor(term no labor,1.00±0.06, vs term delivery,1.29±0.08, p<0.01).In PROM group, there was no difference in median MMP-2 fetal membrane concentrations between women at term delivery and those at term not in labor(term no labor,1.28±0.06, vs term delivery, 1.31±0.08,p>0.05), Similary, fetal membrane concentration of TIMP-2 and ratio of MMP-2/TIMP-2 in fetal membrane were not significantly different. (2)Expression of MMP-9,TIMP-1 and ratio of MMP-9/TIMP-1 in different fetal membrane tissue: In Control group, the median MMP-9 Fetal membrane concentration was significantly higher in women who delivered at term than in women at term not in labor (term no labor, 1.0±0.06, vs term delivery, 1.09±0.03,p<0.01), but there was no difference in median TIMP-1 fetal membrane concentrations between women at term delivery and those at term not in labor(term no labor,1.00±0.05, vs term delivery, 0.97±0.07,p>0.05). ratio of MMP-9/TIMP-1 in fetal membrane was significantly higher in women who delivered at term than in women at term not in labor(term no labor,1.00±0.06, vs term delivery,1.13±0.09, p<0.01). .In PROM group, there was no difference in median MMP-9 fetal membrane concentrations between women at term delivery and those at term not in labor(term no labor,1.12±0.03, vs term delivery, 1.14±0.02,p>0.05), Similary, fetal membrane concentration of TIMP-2 and ratio of MMP-2/TIMP-2 in fetal membrane were not significantly different.