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Blood, 1 August 2008, Vol. 112, No. 3, pp. 585-591. Prepublished online as a Blood First Edition Paper on May 19, 2008; DOI 10.1182/blood-2007-09-111302. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-09-111302v1 112/3/585    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sood, R. Articles by Weiler, H. Search for Related Content PubMed PubMed Citation Articles by Sood, R. Articles by Weiler, H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin Rashmi Sood1, Lynette Sholl2, Berend Isermann1, Mark Zogg1, Shaun R. Coughlin2, and Hartmut Weiler1 1 Blood Research Institute, Blood Center of Wisconsin, Milwaukee; and 2 Cardiovascular Research Institute, University of California, San Francisco 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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