Abstract
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.
Highlights
As detailed below, cultured third trimester decidual cells continue to respond to thrombin with enhanced expression of protease activated receptor (PAR)-mediated endpoints implicated in the genesis of preterm premature rupture of the membranes (PPROM) and preterm delivery (PTD)
While a strong relationship exists between intra-amniotic infection and PPROM, the frequent occurrence of vaginal bleeding indicates that placental abruption is a common antecedent of PPROM [25]
Occult decidual hemorrhage and retrochorionic hematoma formation as reflected in hemosiderin deposition has been reported in nearly 40% of patients with PPROM compared with only about 1% at term (p < 0.01) revealing the robust association that exists between PPROM and abruption
Summary
The relative magnitude of TF expression conforms to a tissue-specific pattern. Low TF levels are present in the liver, spleen, skeletal muscle and thymus where hemostasis appears to depend primarily on the slower acting intrinsic coagulation pathway [6] (Figure 1). The presence of high TF levels in the placenta, skin, heart, lung, brain and uterus is consistent with a requirement for accelerated hemostatic protection utilizing the faster extrinsic coagulation pathway. Adult low-TF mice exhibit hemostatic defects in tissues that normally express high levels of TF such as heart, lung, uterus and placenta [6]. In the mouse uterine wall, expression of high levels of TF in epithelial cells protects against hemorrhage during gestation as well as during the post-partum period. Pregnant low TF mice experience formation of blood pools in the placental labyrinth as well as high fatality rates postpartum [6]
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