The Effect of Progesterone on Tumor Necrosis Factor-α Induced Matrix Metalloproteinase-9 in Human Choriodecidual Membranes

Objective: Progesterone is used to prevent recurrent preterm delivery, however the molecular mechanisms of its effect are incompletely understood. The objective of this study was to determine the effect of progesterone on tumor necrosis factor (TNF)-α-induced matrix metalloproteinase (MMP)-9 activity in human choriodecidual (CD) membranes. Methods: We collected CD membranes from women with uncomplicated term pregnancies who were scheduled for elective cesarean delivery (n=10). CD membranes (1×1 cm) were incubated in tissue culture media at 37°C. We pre-treated the CD membranes with progesterone (P4), 17α- hydroxyprogesterone caproate (17P), promegestone (R5020), or vehicle (ethanol) for 24 hours. The CD membranes were subsequently treated with TNF-α (with continued progesterone treatment) for 48 hours, then media was harvested for measuring MMP-9 activity by zymography and total protein was isolated from CD membrane tissues for MMP-9 expression by western blot analysis. Results: P4, 17P, and R5020 significantly reduced TNF-α-induced MMP-9 activity in fetal membrane tissue samples (P=0.0078, P=0.0156, and P=0.0391, respectively) by zymography. Western blot analysis also showed decreased expression of MMP-9 in progesterone pretreated groups (P=0.0313). Conclusion: Progesterone reduces TNF-α-induced MMP-9 activity in human CD membranes. These findings may provide further support for the role of progesterone in preventing preterm birth. KCI Citation Count: 0