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 factor (TF) in the absence of murine TF to analyze the role of TF in gestation. Low-TF female mice had a 14-18% incidence of fatal postpartum uterine hemorrhage, 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 fatal midgestational hemorrhage (n = 41), whereas no fatal midgestational hemorrhages 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 females were abnormal and contained numerous maternal blood pools in the labyrinth. Placentas of TF null embryos surviving beyond embryonic day 10.5 exhibited similar defects. The mouse maternal-embryonic placental barrier consists of four cellular layers (layers I, II, and III and endothelial cells), where layer I lines the maternal lacunae. Comparison of TF-deficient placentas with control placentas by immunohistochemical and ultrastructural analyses revealed thinning of layer I and a reduction in the number of cellular contacts of layer I trophoblasts spanning the maternal blood space between adjacent trabeculae. These structural changes in low-TF and TF null placentas result in enlarged maternal lacunae, as determined by morphometric analysis, and placental hemorrhage, which leads to midgestational death of low-TF female mice. This study demonstrated that TF is required for uterine hemostasis and revealed an unexpected role of TF in the maintenance of the placental labyrinth.
Erlich
J
J
Departments of Immunology and Vascular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Parry
G C
GC
Fearns
C
C
Muller
M
M
Carmeliet
P
P
Luther
T
T
Mackman
N
N
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D006487:Hemostasis; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000002:abnormalities / Q000098:blood supply / Q000502:physiology*; D011247:Pregnancy; D011644:Puerperal Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013925:Thromboplastin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014592:Uterine Hemorrhage / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D014599:Uterus / Q000002:abnormalities / Q000098:blood supply / Q000502:physiology*
D013925:Thromboplastin