Intersection of regulatory pathways controlling hemostasis and hemochorial placentation

Significance Trophoblast cell–guided uterine spiral artery remodeling is a key event in successful hemochorial placentation. Connections between coagulopathies and diseases of placentation are compelling. Tissue factor pathway inhibitor (TFPI) is a prominent regulator of blood coagulation and an intriguing constituent of trophoblast cells situated at the uterine–placental interface. The actions of TFPI extend beyond controlling hemostasis and directly affect trophoblast cell development. TFPI facilitates the differentiation of rat and human trophoblast stem cells into the invasive/extravillous trophoblast cell lineage and promotes intrauterine trophoblast invasion and trophoblast-guided uterine spiral artery remodeling at the maternal–fetal interface. Thus, TFPI is a conserved regulator of a fundamental event determining the efficacy of the hemochorial placenta.