Mechanisms of abruption-induced premature rupture of the fetal membranes: Thrombin enhanced decidual matrix metalloproteinase-3 (stromelysin-1) expression

Objective: The aim of the study was to evaluate thrombin and progestin effects oil matrix metalloproteinase-3 expression in term decidual cells as a mechanism of abruption-related preterm delivery. Study design: Decidual cells were isolated by standard techniques, purified to homogeneity, Grown to confluence, and passaged. Cultures were printed with 10(-8) M estradiol or estradiol Plus 10(-7) pro.-estin and then incubated in a defined medium with corresponding steroid(s) plus or minus thrombin or the protease-activated thrombin receptor-1 agonist for 24 hours. Secreted matrix metalloproteinase-3 levels were assessed by enzyme-linked immunosorbent assay, and immunoblotting and messenger RNA levels were measured by Northern blotting and quantitative reverse transcription-polymerase chain reaction. Results: Immnuoreactive matrix metalloproteinase-3 levels were inhibited 66% by estradiol plus progestin versus estradiol (P < .05). Thrombin elicited a dose-dependent reversal in this progestin inhibition, producing a 2.5-fold increase at 2.5 U/mL (P < .05) that attained 33% of matrix metalloproteinase-3 levels in parallel incubations with estradiol Plus thrombin. Protease-activated thrombin receptor-1 agonist mimicked 60% of thrombin-enhanced matrix metalloproteinase-3 Output. Immunoblotting validated the enzyme-linked immunosorbent assay results. Northern blotting and quantitative reverse transcription-polymerase chain reaction demonstrated corresponding effects oil steady-state messenger RNA levels. Conclusion: Abruption-generated thrombin promotes preterm delivery by mediating fetal membrane extracellular matrix degradation via enhanced decidual cell matrix metalloproteinase-3 expression, whereas progesterone blunts this thrombin-induced effect. (C) 2004 Elsevier Inc. All rights reserved.