An increased molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 is associated with decreased tensile strength of human fetal membranes in uncomplicated labor.
Links MMP-9 to fetal membrane weakening in labor; hypothesis-generating for rupture mechanisms and needs clinical validation.
In Brief Objective To analyze the relation between tensile strength and levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 at a number of sites in human fetal membranes. Methods Tensile strengths of fetal membranes from five women who delivered vaginally at term were measured by the method of modified force application. A piece of membrane at each measured site was then dissected, and the levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 were measured by sandwich enzyme immunoassay. The relationship between tensile strength and enzyme levels was evaluated by Scheffé F test at a total of 81 sites on the five membranes. Results The mean tensile strength of the membranes was 45.3 ± 19.8 (mean ± standard deviation) mmHg/0.3 mm2 (n = 81). When the measured sites were divided according to tensile strength into four groups (<25, 25–49, 50–74, and ≥75 mmHg/0.3 mm2), the level of matrix metalloproteinase-9 (0.72 ± 0.82 nmol/g protein, n = 12) in the less than 25 mmHg/0.3 mm2 group was significantly higher than the other groups (0.35 ± 0.22, 0.28 ± 0.15, and 0.15 ± 0.08 nmol/g protein; n = 39, 23, and 7, respectively). The significance level was still higher when the molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 was used for comparison. Conclusion An increased molar ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 might be related to decreased tensile strength of human fetal membranes in uncomplicated labor. Joints of low tensile strength in human fetal membranes correspond to locations with enhanced matrix metalloproteinase-9 production relative to tissue inhibitor of metalloproteinase-1.
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Uchide et al. (2000) studied this question.
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