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The purpose of this study was to investigate the expression of matrix metalloproteinase-8 by human fetal membranes during labor. Fetal membranes were obtained from women who underwent normal labor or elective cesarean delivery at term. Matrix metalloproteinase-8 levels in fetal membranes were determined by enzyme-linked immunosorbent assay and Western blot; the expression of the matrix metalloproteinase-8 gene was detected by reverse transcription-polymerase chain reaction. Immunohistochemistry and in situ hybridization was performed to localize matrix metalloproteinase-8 protein and messenger RNA in intact membranes. Matrix metalloproteinase-8 protein levels were increased 5-fold in fetal membranes from labor compared with membranes that were obtained from cesarean delivery. Western blots confirmed the presence of matrix metalloproteinase-8 in protein extracts. Reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemistry demonstrated that matrix metalloproteinase-8 messenger RNA and protein were expressed almost exclusively in the chorion after labor. We conclude that matrix metalloproteinase-8 is produced primarily by chorionic cells in human fetal membranes and that the level of matrix metalloproteinase-8 protein and messenger RNA expression in fetal membranes increases during labor.