During human pregnancy, progesterone induced decidual cells protect against hemorrhage: 1) as endovascular trophoblast breech and remodel uterine blood vessels;and 2) in the third stage of labor following preterm and term delivery. De- cidual cells promote hemostasis through enhanced expression of tissue factor (TF), the primary initiator of hemostasis via thrombin generation, and plasminogen activator inhibitor-1, which inactivates tissue type plasminogen activator, the primary fibrinolytic agent. Abruptions (decidual hemorrhage) produce excess thrombin which acts as autocrine/paracrine inducer of decidual cell expressed matrix metalloproteinases and of neutrophil chemoattractant and activator, interleukin-8. The latter mediates aseptic abruption-related neutrophil infiltration. During abruptions, decidual cell and neutrophil-derived proteases effectively degrade the decidual and fetal membrane extracellular matrix to promote preterm premature rupture of the membranes and preterm delivery (PTD). Decidual cell-derived thrombin weakens the amniotic membrane and lowers decidual cell-expressed progesterone receptor levels by increasing phospho-ERK1/2 signaling. The resulting functional progesterone withdrawal accompanies PTD.
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