Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin. Blood 2008 Aug 01;112(3):585-91
Date
05/21/2008Pubmed ID
18490515Pubmed Central ID
PMC2481555DOI
10.1182/blood-2007-09-111302Scopus ID
2-s2.0-50949133923 (requires institutional sign-in at Scopus site) 33 CitationsAbstract
Absence of the blood coagulation inhibitor thrombomodulin (Thbd) from trophoblast cells of the mouse placenta causes a fatal arrest of placental morphogenesis. The pathogenesis of placental failure requires tissue factor, yet is not associated with increased thrombosis and persists in the absence of fibrinogen. Here, we examine the role of alternative targets of coagulation that might contribute to the placental failure and death of Thbd(-/-) embryos. We demonstrate that genetic deficiency of the protease-activated receptors, Par1 or Par2, in the embryo and trophoblast cells does not prevent the death of Thbd(-/-) embryos. Similarly, genetic ablation of the complement pathway or of maternal immune cell function does not decrease fetal loss. In contrast, Par4 deficiency of the mother, or the absence of maternal platelets, restores normal development in one-third of Thbd-null embryos. This finding generates new evidence implicating increased procoagulant activity and thrombin generation in the demise of thrombomodulin-null embryos, and suggests that platelets play a more prominent role in placental malfunction associated with the absence of thrombomodulin than fibrin formation. Our findings demonstrate that fetal prothrombotic mutations can cause localized activation of maternal platelets at the feto-maternal interface in a mother with normal hemostatic function.
Author List
Sood R, Sholl L, Isermann B, Zogg M, Coughlin SR, Weiler HAuthors
Rashmi Sood PhD Associate Professor in the Pathology department at Medical College of WisconsinHartmut Weiler PhD Associate Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBlood Coagulation
Blood Platelets
Embryo, Mammalian
Female
Maternal-Fetal Exchange
Mice
Mice, Knockout
Mothers
Placenta Diseases
Pregnancy
Receptors, Proteinase-Activated
Thrombomodulin
Thrombophilia