The decidua regulates hemostasis in human endometrium

Survival of the implanting human blastocyst requires that trophoblasts gain access to the maternal circulation. This is initially achieved when syncytiotrophoblasts breach endometrial capillaries and venules. Subsequently, extravillous cytotrophoblasts penetrate the spiral arteries to induce their morphological transformation into high-flow low-resistance vessels. This process provides the embryo with a requisite source of oxygen and nutrients, but risks decidual hemorrhage leading to abortion and abruption. Endovascular trophoblast invasion occurs within a matrix of decidualizing endometrial stromal cells. These decidual cells are temporally and spatially positioned to create a local hemostatic milieu which can counteract the threat of hemorrhage. Prior studies from our laboratory have established that decidual cells of luteal phase and pregnant endometrium express two crucial modulators of hemostasis: 1) tissue factor (TF), the primary initiator of hemostasis via factor Xa activation; and 2) plasminogen activator inhibitor type 1 (PAI-1), the fast inhibitor of the primary fibrinolytic agent, tissue type plasminogen activator. This coordinate increase in TF and PAI-1 expression provides a mechanism by which decidual cells control local hemostasis during endovascular trophoblast invasion. Cultures of human endometrial stromal cells and decidual cells isolated from first trimester endometrium demonstrate that progestins enhance TF and PAI-1 protein and mXNA expression via the induction of crucial intermediate transcription factors. Integration of these in vivo observations and in vitro studies suggest a model by which decidua acts to maintain hemostasis during implantation and placentation.