Tissue factor is required for uterine hemostasis and maintenance of the placental labyrinth during gestation

We employed a novel mouse line that expresses low levels of human tissue fa ctor (TF) in the absence of murine TF to analyze the role of TF in gestatio n. Low-TF female mice had a 14-18% incidence of fatal postpartum uterine he morrhage, suggesting that TF plays an important role in uterine hemostasis. Low-TF female mice mated with low-TF male mice had a 42% incidence of fata l midgestational hemorrhage (n = 41), whereas no fatal midgestational hemor rhages were observed in low-TF female mice mated with wild-type male mice ( n = 43). Placentas of low-TF embryos from both low-TF and normal (+/-) TF f emales were abnormal and contained numerous maternal blood pools in the lab yrinth. Placentas of TF null embryos surviving beyond embryonic day 10.5 ex hibited similar defects. The mouse maternal-embryonic placental barrier con sists of four cellular layers (layers I, II; and III and endothelial cells) , where layer I lines the maternal lacunae, Comparison of TF-deficient plac entas with control placentas by immunohistochemical and ultrastructural ana lyses revealed thinning of layer I and a reduction in the number of cellula r contacts of layer I trophoblasts spanning the maternal blood space betwee n adjacent trabeculae, These structural changes in low-TF and TF null place ntas result in enlarged maternal lacunae, as determined by morphometric ana lysis, and placental hemorrhage, which leads to midgestational death of low -TF female mice. This study demonstrated that TF is required for uterine he mostasis and revealed an unexpected role of TF in the maintenance of the pl acental labyrinth.