The endothelial protein C receptor plays an essential role in the maintenance of pregnancy
| Autor: | Rashmi Sood, Abril Solis Sigala, Qiuhui Yang, Kristen L. Chen, Min Zhan, Michelle M. Castillo, Dosia T. McKinney, Jason A. Jarzembowski |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Placenta Diseases and Disorders Thrombophilia Bioinformatics Andrology Mice 03 medical and health sciences 0302 clinical medicine Pregnancy medicine Animals Platelet Platelet activation Abruptio Placentae Research Articles Clotting factor Fetus Endothelial protein C receptor Maternal thrombophilia Multidisciplinary Placental abruption business.industry SciAdv r-articles Endothelial Protein C Receptor Thrombosis medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures Uteroplacental Circulation Maternal death Female business Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.abb6196 |
| Popis: | Mice reveal a link between maternal or fetal thrombophilia, uteroplacental thrombosis, hemorrhage, and placental abruption. Placenta-mediated pregnancy complications are a major challenge in the management of maternal-fetal health. Maternal thrombophilia is a suspected risk factor, but the role of thrombotic processes in these complications has remained unclear. Endothelial protein C receptor (EPCR) is an anticoagulant protein highly expressed in the placenta. EPCR autoantibodies and gene variants are associated with poor pregnancy outcomes. In mice, fetal EPCR deficiency results in placental failure and in utero death. We show that inhibition of molecules involved in thrombin generation or in the activation of maternal platelets allows placental development and embryonic survival. Nonetheless, placentae exhibit venous thrombosis in uteroplacental circulation associated with neonatal death. In contrast, maternal EPCR deficiency results in clinical and histological features of placental abruption and is ameliorated with concomitant Par4 deficiency. Our findings unveil a causal link between maternal thrombophilia, uterine hemorrhage, and placental abruption and identify Par4 as a potential target of therapeutic intervention. |
| Databáze: | OpenAIRE |
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