Obstetrics, Gynecology and Reproduction

Advanced search


Full Text:


Microvesicles (MVs), including microparticles and exosomes, are secreted from a variety of cells. They are present in the blood circulation under normal physiological conditions, and their levels increase in a wide range of disease states. MVs contain proteins, growth and apoptotic factors, DNA fragments, microRNAs as well as messenger RNAs (mRNAs); therefore, they may function as regulators in cell-cell communication and mediators of cell signaling during multiple biological processes. The current review focuses on the role of MVs in healthy pregnancy and gestational vascular complications and discusses the involvement of MVs in thrombosis, hemostasis and cell function that overall reflect the placental-maternal crosstalk.

About the Authors

A. Aharon
Microvesicles Research Laboratory, Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
Russian Federation

PhD, Head, Microvesicles Research Laboratory, Thrombosis and Hemostasis Unit, Department of Hematology, Rambam Health Care Campus, P.O. Box 9602, Haifa 31096, Israel. Phone: +972-54-8004600. Fax: +972 4 777 3886

B. Brenner
Microvesicles Research Laboratory, Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
Russian Federation

MD, Professor, Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel


1. Valadi H., Ekstrom K, Bossios A., et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007 Jun; 9 (6): 654-9.

2. Piccin A., Murphy W.G., Smith O.P. Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 2007 May; 21 (3): 157-71.

3. Simpson R.J., Jensen S.S., Lim J.W. Proteomic profiling of exosomes: current perspectives. Proteomics 2008 Oct; 8 (19): 4083-99.

4. Cocucci E., Racchetti G., Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009 Feb; 19 (2): 43-51.

5. Denzer K., Kleijmeer M.J., Heijnen H.F., et al. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci. 2000 Oct; 113 Pt 19: 3365-74.

6. Schara K., Jansa V., Sustar V. et al. Mechanisms for the formation of membranous nanostructures in cell-to-cell communication. Cell Mol Biol Lett. 2009; 14 (4): 636-56.

7. Essayagh S. Xuereb J.M., Terrisse A.D. et al. Microparticles from apoptotic monocytes induce transient platelet recruitment and tissue factor expression by cultured human vascular endothelial cells via a redox-sensitive mechanism. Thromb Haemost. 2007 Oct; 98 (4): 831-7.

8. Simak J., Gelderman M.P. Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfus Med Rev. 2006 Jan; 20 (1): 1-26.

9. Del Conde I., Shrimpton C.N., Thiagarajan P. et al. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood. 2005 Sep 1; 106 (5): 1604-11.

10. Burger D., Schock S., Thompson C.S. et al. Microparticles: biomarkers and beyond. Clin Sci (Lond). 2013 Apr; 124 (7): 423-41.

11. Aharon A., Brenner B. Microparticles and pregnancy complications. Thromb Res. 2011 Feb; 127 Suppl 3: 67-71.

12. Hristov M., Erl W., Linder S. et al. Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood. 2004 Nov 1; 104 (9): 2761-6.

13. Janowska-Wieczorek A., Wysoczynski M., Kijowski J. et al. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer. 2005 Feb 20; 113 (5): 752-60.

14. Segura E., Guerin C., Hogg N. et al. CD8+dendritic cells use LFA-1 to capture MHCpeptide complexes from exosomes in vivo. J Immunol. 2007 Aug 1; 179 (3): 1489-96.

15. Morelli A.E., Larregina A.T., Shufesky W.J. et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood. 2004 Nov 15; 104 (10): 3257-66.

16. Chou J., Mackman N., Merrill-Skoloff G. et al. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood. 2004 Nov 15; 104 (10): 3190-7.

17. Lopez J.A., del Conde I., Shrimpton C.N. Receptors, rafts, and microvesicles in thrombosis and inflammation. J Thromb Haemost. 2005 Aug; 3 (8): 1737-44.

18. Furie B., Furie B.C. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol Med. 2004 Apr; 10 (4): 171-8.

19. Diamant M., Tushuizen M.E., Sturk A. et al. Cellular microparticles: new players in the field of vascular disease? Eur J Clin Invest. 2004 Jun; 34 (6): 392-401.

20. Furie B., Furie B.C. Mechanisms of thrombus formation. N Engl J Med. 2008 Aug 28; 359 (9): 938-49.

21. Tsimerman G., Roguin A., Bachar A. et al. Involvement of microparticles in diabetic vascular complications. Thromb Haemost. 2011 Aug; 106 (2): 310-21.

22. Aharon A., Brenner B. Microparticles, thrombosis and cancer. Best Pract Res. Clin Haematol. 2009 Mar; 22 (1): 61-9.

23. Tzoran I., Rebibo-Sabbah A., Brenner B., et al. Disease dynamics in patients with acute myeloid leukemia: New biomarkers. Exp Hematol. 2015 Nov; 43 (11): 936-43.

24. Martinez M.C., Tesse A., Zobairi F. et al. Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol. 2005 Mar; 288 (3): H1004-9.

25. Campello E., Spiezia L., Radu C.M. et al. Circulating microparticles in carriers of prothrombin G20210A mutation. Thromb Haemost. 2014 Sep 2; 112 (3): 432-7.

26. Campello E., Spiezia L., Radu C.M. et al. Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S. Thromb Haemost. 2015 Dec 22; 115 (1): 81-8.

27. Breen K.A., Sanchez K., Kirkman N. et al. Endothelial and platelet microparticles in patients with antiphospholipid antibodies. Thromb Res. 2015 Feb; 135 (2): 368-74.

28. Dinkla S., Brock R., Joosten I. et al. Gateway to understanding microparticles: standardized isolation and identification of plasma membrane-derived vesicles. Nanomedicine (Lond). 2013 Oct; 8 (10): 1657-68.

29. Radu C.M., Campello E., Spiezia L. et al. Origin and levels of circulating microparticles in normal pregnancy: A longitudinal observation in healthy women. Scand J Clin Lab Invest. 2015 Oct; 75 (6): 487-95.

30. Luo S.S., Ishibashi O., Ishikawa G. et al. Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes. Biol Reprod. 2009 Oct; 81 (4): 717-29.

31. Katzenell S., Shomer E., Zipori Y. et al. Characterization of negatively charged phospholipids and cell origin of microparticles in women with gestational vascular complications. Thromb Res. 2012 Sep; 130 (3): 479-84.

32. Gonzalez-Quintero V.H., Jimenez J.J., Jy W. et al. Elevated plasma endothelial microparticles in preeclampsia. Am J Obstet Gynecol. 2003 Aug; 189 (2): 589-93.

33. Petrozella L., Mahendroo M., Timmons B. et al. Endothelial microparticles and the antiangiogenic state in preeclampsia and the postpartum period. Am J Obstet Gynecol. 2012 Aug; 207 (2): 140 e20-6.

34. Salem M., Kamal S., El Sherbiny W. et al. Flow cytometric assessment of endothelial and platelet microparticles in preeclampsia and their relation to disease severity and Doppler parameters. Hematology. 2015 Apr; 20 (3): 154-9.

35. Meziani F., Tesse A., David E. et al. Shed membrane particles from preeclamptic women generate vascular wall inflammation and blunt vascular contractility. Am J Pathol. 2006 Oct; 169 (4): 1473-83.

36. Lok C.A., Jebbink J., Nieuwland R. et al. Leukocyte activation and circulating leukocytederived microparticles in preeclampsia. Am J Reprod Immunol. 2009 May; 61 (5): 346-59.

37. Ling L., Huang H., Zhu L. et al. Evaluation of plasma endothelial microparticles in preeclampsia. J Int Med Res. 2014 Feb; 42 (1): 42-51.

38. Patil R., Ghosh K., Satoskar P. et al. Elevated procoagulant endothelial and tissue factor expressing microparticles in women with recurrent pregnancy loss. PLoS One. 2013; 8 (11): e81407.

39. Pasquier E., De Saint Martin L., Bohec C. et al. Unexplained pregnancy loss: a marker of basal endothelial dysfunction? Fertil Steril. 2013 Oct; 100 (4): 1013-7.

40. Laude I., Rongieres-Bertrand C., Boyer-Neumann C. et al. Circulating procoagulant microparticles in women with unexplained pregnancy loss: a new insight. Thromb Haemost. 2001 Jan; 85 (1): 18-21.

41. Aharon A., Katzenell S., Tamari T. et al. Microparticles bearing tissue factor and tissue factor pathway inhibitor in gestational vascular complications. J Thromb Haemost. 2009 Jun; 7 (6): 1047-50.

42. Aharon A., Lanir N., Drugan A. et al. Placental TFPI is decreased in gestational vascular complications and can be restored by maternal enoxaparin treatment. J Thromb Haemost. 2005 Oct; 3 (10): 2355-7.

43. Goswami D., Tannetta D.S., Magee L.A. et al. Excess syncytiotrophoblast microparticle shedding is a feature of early-onset preeclampsia, but not normotensive intrauterine growth restriction. Placenta. 2006 Jan; 27 (1): 56-61.

44. Record M. Intercellular communication by exosomes in placenta: a possible role in cell fusion? Placenta. 2014 May; 35 (5): 297-302.

45. Orozco A.F., Jorgez C.J., Ramos-Perez W.D. et al. Placental release of distinct DNA-associated micro-particles into maternal circulation: reflective of gestation time and preeclampsia. Placenta. 2009 Oct; 30 (10): 891-7.

46. Vanwijk M.J., Svedas E., Boer K. et al. Isolated microparticles, but not whole plasma, from women with preeclampsia impair endotheliumdependent relaxation in isolated myometrial arteries from healthy pregnant women. Am J Obstet Gynecol. 2002 Dec; 187 (6): 1686-93.

47. Messerli M., May K., Hansson S.R., et al. Fetomaternal interactions in pregnancies: placental microparticles activate peripheral blood monocytes. Placenta. 2010 Feb; 31 (2): 106-12.

48. Aharon A., Brenner B., Katz T. et al. Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis. Thromb Haemost. 2004 Oct; 92 (4): 776-86.

49. Marques F.K., Campos F.M., Sousa L.P. et al. Association of microparticles and preeclampsia. Mol Biol Rep. 2013 Jul; 40 (7): 4553-9.

50. Laresgoiti-Servitje E. A leading role for the immune system in the pathophysiology of preeclampsia. J Leukoc Biol. 2013 Aug; 94 (2): 247-57.

51. Gardiner C., Tannetta D.S., Simms C.A. et al. Syncytiotrophoblast microvesicles released from pre-eclampsia placentae exhibit increased tissue factor activity. PLoS One. 2011; 6 (10): e26313.

52. Raghupathy R. Cytokines as key players in the pathophysiology of preeclampsia. Med Princ Pract. 2013; 22 Suppl 1: 8-19.

53. Shomer E., Katzenell S., Zipori Y. et al. Microvesicles of women with gestational hypertension and preeclampsia affect human trophoblast fate and endothelial function. Hypertension. 2013 Nov; 62 (5): 893-8.

54. Germain S.J., Sacks G.P., Sooranna S.R. et al. Systemic inflammatory priming in normal pregnancy and preeclampsia: the role of circulating syncytiotrophoblast microparticles. J Immunol. 2007 May 1; 178 (9): 5949-56.

55. Tesse A., Meziani F., David E. et al. Microparticles from preeclamptic women induce vascular hyporeactivity in vessels from pregnant mice through an overproduction of NO. Am J Physiol Heart Circ Physiol. 2007 Jul; 293 (1): H520-5.

56. Ambros V., Lee RC. Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning. Methods Mol Biol. 2004; 265: 131-58.

57. Esquela-Kerscher A., Slack F.J. Oncomirs –microRNAs with a role in cancer. Nat Rev Cancer. 2006 Apr; 6 (4): 259-69.

58. Morales-Prieto D.M., Ospina-Prieto S., Chaiwangyen W. et al. Pregnancy-associated miRNA-clusters. J Reprod Immunol. 2013 Mar; 97 (1): 51-61.

59. Hannafon B.N., Ding W.Q. Intercellular communication by exosome-derived microRNAs in cancer. Int J Mol Sci. 2013; 14 (7): 14240-69.

60. Stenqvist A.C., Nagaeva O., Baranov V. et al. Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the fetus. J Immunol. 2013 Dec 1; 191 (11): 5515-23.

61. Thum T., Gross C., Fiedler J. et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008 Dec 18; 456 (7224): 980-4.

62. Thum T., Galuppo P., Wolf C. et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007 Jul 17; 116 (3): 258-67.

63. Mitchell P.S., Parkin R.K., Kroh E.M. et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29; 105 (30): 10513-8.

64. Hunter M.P., Ismail N., Zhang X. et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One. 2008; 3 (11): e3694.

65. Dangwal S., Thum T. microRNA therapeutics in cardiovascular disease models. Annu Rev Pharmacol Toxicol. 2014; 54: 185-203.

66. Diehl P., Fricke A., Sander L. et al. Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res. 2012 Mar 15; 93 (4): 633-44.

67. Mittelbrunn M., Gutierrez-Vazquez C., Villarroya-Beltri C. et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun. 2011; 2: 282.


For citations:

Aharon A., Brenner B. MICROVESICLES AND THROMBOSIS IN OBSTETRIC-GYNECOLOGICAL COMPLICATIONS. Obstetrics, Gynecology and Reproduction. 2016;10(1):5-10. (In Russ.)

Views: 599

ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)