Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans
Background: Amniotic fluid (AF) plays a key role in fetal development, yet the evolving composition of AF and its effects on hemostasis and thrombosis are poorly understood. Objectives: To characterize the procoagulant properties of AF as a function of gestation in humans and nonhuman primates. Meth...
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Elsevier
2025-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037924003716 |
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| author | Chih Jen Yang Lyndsey E. Shorey-Kendrick Cristina Puy Ashley E. Benson Phillip A. Wilmarth Ashok P. Reddy Keith D. Zientek Kilsun Kim Adam Crosland Chaevien S. Clendinen Lisa M. Bramer Olivia L. Hagen Helen H. Vu Joseph E. Aslan Owen J.T. McCarty Joseph J. Shatzel Brian P. Scottoline Jamie O. Lo |
| author_facet | Chih Jen Yang Lyndsey E. Shorey-Kendrick Cristina Puy Ashley E. Benson Phillip A. Wilmarth Ashok P. Reddy Keith D. Zientek Kilsun Kim Adam Crosland Chaevien S. Clendinen Lisa M. Bramer Olivia L. Hagen Helen H. Vu Joseph E. Aslan Owen J.T. McCarty Joseph J. Shatzel Brian P. Scottoline Jamie O. Lo |
| author_sort | Chih Jen Yang |
| collection | DOAJ |
| description | Background: Amniotic fluid (AF) plays a key role in fetal development, yet the evolving composition of AF and its effects on hemostasis and thrombosis are poorly understood. Objectives: To characterize the procoagulant properties of AF as a function of gestation in humans and nonhuman primates. Methods: We analyzed the proteomes, lipidomes, and procoagulant properties of AF obtained by amniocentesis from rhesus macaque and human pregnancies at gestational age-matched time points. Results: When added to human plasma, both rhesus and human AF accelerated clotting time and fibrin generation. We identified proteomic modules associated with clotting time and enriched for coagulation-related pathways. Proteins known to be involved in hemostasis were highly correlated with each other, and their intensity of expression varied across gestation in both rhesus and humans. Inhibition of the contact pathway did not affect the procoagulant effect of AF. Blocking tissue factor pathway inhibitor reversed the ability of AF to block the generation of activated factor X. The prothrombinase activity of AF was inhibited by phospholipid inhibitors. The levels of phosphatidylserine in AF were inversely correlated with clotting time. AF promoted platelet activation and secretion in plasma. Conclusion: Overall, our findings reveal that the addition of AF to plasma enhances coagulation in a manner dependent on phospholipids as well as the presence of proteases and other proteins that directly regulate coagulation. We describe a correlation between clotting time and expression of coagulation proteins and phosphatidylserine in both rhesus and human AF, supporting the use of rhesus models for future studies of AF biology. |
| format | Article |
| id | doaj-art-61831d97052c4c1a9107c856777743b1 |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-61831d97052c4c1a9107c856777743b12025-01-26T05:04:32ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102676Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humansChih Jen Yang0Lyndsey E. Shorey-Kendrick1Cristina Puy2Ashley E. Benson3Phillip A. Wilmarth4Ashok P. Reddy5Keith D. Zientek6Kilsun Kim7Adam Crosland8Chaevien S. Clendinen9Lisa M. Bramer10Olivia L. Hagen11Helen H. Vu12Joseph E. Aslan13Owen J.T. McCarty14Joseph J. Shatzel15Brian P. Scottoline16Jamie O. Lo17Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USA; Department of Emergency Medicine, Tri-Service General Hospital, National Defensive Medical Center, Taipei, TaiwanDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USADivision of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon, USAProteomics Shared Resources, Oregon Health & Science University, Portland, Oregon, USAProteomics Shared Resources, Oregon Health & Science University, Portland, Oregon, USAProteomics Shared Resources, Oregon Health & Science University, Portland, Oregon, USAProteomics Shared Resources, Oregon Health & Science University, Portland, Oregon, USADivision of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon, USAThe Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USABiological Systems Directorate, Pacific Northwest National Laboratory, Richland, Washington, USADivision of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USAKnight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USA; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USADivision of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA; Division of Neonatology, Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, USADivision of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon, USA; Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA; Correspondence Jamie Lo, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L458 Portland, OR 97239, USA.Background: Amniotic fluid (AF) plays a key role in fetal development, yet the evolving composition of AF and its effects on hemostasis and thrombosis are poorly understood. Objectives: To characterize the procoagulant properties of AF as a function of gestation in humans and nonhuman primates. Methods: We analyzed the proteomes, lipidomes, and procoagulant properties of AF obtained by amniocentesis from rhesus macaque and human pregnancies at gestational age-matched time points. Results: When added to human plasma, both rhesus and human AF accelerated clotting time and fibrin generation. We identified proteomic modules associated with clotting time and enriched for coagulation-related pathways. Proteins known to be involved in hemostasis were highly correlated with each other, and their intensity of expression varied across gestation in both rhesus and humans. Inhibition of the contact pathway did not affect the procoagulant effect of AF. Blocking tissue factor pathway inhibitor reversed the ability of AF to block the generation of activated factor X. The prothrombinase activity of AF was inhibited by phospholipid inhibitors. The levels of phosphatidylserine in AF were inversely correlated with clotting time. AF promoted platelet activation and secretion in plasma. Conclusion: Overall, our findings reveal that the addition of AF to plasma enhances coagulation in a manner dependent on phospholipids as well as the presence of proteases and other proteins that directly regulate coagulation. We describe a correlation between clotting time and expression of coagulation proteins and phosphatidylserine in both rhesus and human AF, supporting the use of rhesus models for future studies of AF biology.http://www.sciencedirect.com/science/article/pii/S2475037924003716amniotic fluidcoagulation factorshemostasispregnancyrhesus macaque |
| spellingShingle | Chih Jen Yang Lyndsey E. Shorey-Kendrick Cristina Puy Ashley E. Benson Phillip A. Wilmarth Ashok P. Reddy Keith D. Zientek Kilsun Kim Adam Crosland Chaevien S. Clendinen Lisa M. Bramer Olivia L. Hagen Helen H. Vu Joseph E. Aslan Owen J.T. McCarty Joseph J. Shatzel Brian P. Scottoline Jamie O. Lo Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans Research and Practice in Thrombosis and Haemostasis amniotic fluid coagulation factors hemostasis pregnancy rhesus macaque |
| title | Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans |
| title_full | Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans |
| title_fullStr | Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans |
| title_full_unstemmed | Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans |
| title_short | Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans |
| title_sort | characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans |
| topic | amniotic fluid coagulation factors hemostasis pregnancy rhesus macaque |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924003716 |
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