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Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin
- Source :
- Blood. 112:585-591
- Publication Year :
- 2008
- Publisher :
- American Society of Hematology, 2008.
-
Abstract
- 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.
- Subjects :
- Blood Platelets
medicine.medical_specialty
Placenta Diseases
Thrombomodulin
Receptors, Proteinase-Activated
Immunology
Mothers
Hemostasis, Thrombosis, and Vascular Biology
Biochemistry
Fibrin
Andrology
Mice
Tissue factor
Thrombin
Pregnancy
Internal medicine
Placenta
medicine
Animals
Thrombophilia
Platelet
Blood Coagulation
Maternal-Fetal Exchange
Mice, Knockout
biology
Trophoblast
Cell Biology
Hematology
Embryo, Mammalian
medicine.anatomical_structure
Endocrinology
Coagulation
embryonic structures
biology.protein
Female
medicine.drug
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....ec0420804a810d6ea0a2630941e57238