РОЛЬ ВЗАИМОДЕЙСТВИЯ ЭКСТРАКЛЕТОЧНЫХ МИКРОВЕЗИКУЛ ТРОФОБЛАСТА С КЛЕТКАМИ ИММУННОЙ СИСТЕМЫ И ЭНДОТЕЛИЯ В ПАТОГЕНЕЗЕ ПРЕЭКЛАМПСИИ

Преэклампсия является мультисистемным заболеванием, возникающим во второй половине беременности и характеризующимся развитием гипертензии и протеинурии. Преэклампсия до сих пор остается одной из основных причин материнской и неонатальной заболеваемости и смертности. Как полагают, преэклампсия является результатом сложных взаимодействий материнских и плацентарных факторов, однако непосредственная патофизиология этого синдрома остается неясной. Межклеточные взаимодействия являются основой фетоплацентарного развития при физиологически протекающей беременности. Один из механизмов межклеточных взаимодействий связан с выбросом клетками ограниченных мембраной экстраклеточных микровезикул. Концентрация и молекулярный состав экстраклеточных везикул в биологических жидкостях зависят от продуцирующих их клеток, а также стимулов, инициирующих их продукцию. Исследование экстраклеточных везикул при преэклампсии фокусируется на частицах, вырабатываемых клетками сердечно-сосудистой системы матери (эндотелий, гладкие мышцы сосудов) и крови (эритроциты, лейкоциты и тромбоциты), а также клетками синцитиотрофобласта. Изменения в концентрации и молекулярном составе этих экстраклеточных везикул могут вносить вклад в патофизиологию преэклампсии благодаря усилению провоспалительного и прокоагуляционного состояния при беременности. Настоящий обзор посвящен, в первую очередь, характеристике экстраклеточных везикул, продуцируемых синцитиотрофобластом, а также возможной роли их взаимодействия с клетками материнской иммунной системы, эндотелиальными клетками и тромбоцитами в процессе развития преэклампсии. Понимание роли экстраклеточных везикул синцитиотрофобласта в патогенезе преэклампсии могло бы открыть возможности использования полученных данных для ранней и неинвазивной диагностики плацентарных нарушений, а также для прогноза развития этого заболевания.

преэклампсия, гипертензия, плацента, трофобласт, микровезикулы, межклеточные взаимодействия

1. Айламазян Э.К., Степанова О.И., Сельков С.А., Соколов Д.И. Клетки иммунной системы матери и клетки трофобласта: «конструктивное сотрудничество» ради достижения совместной цели // Вестник РАМН, 2013. Т. 68, № 11. С. 12-21. [Ailamazyan E.K., Stepanova O.I., Selkov S.A., Sokolov D.I. Cells of immune system of mother аnd trophoblast cells: constructive cooperation for the sake of achievement of the joint purpose. Vestnik RAMN = Annals of the Russian Academy of Medical Sciences, 2013, Vol. 68, no. 11, pp. 12-21. (In Russ.)]

2. Милованов А.П., Волощук И.Н. Депортированный синцитиотрофобласт и плацентарные микрочастицы в организме матери при нормальной беременности и преэклампсии (28 лет спустя) // Архив патологии, 2017. Т. 79, № 1. С. 61-67. [Milovanov A.P., Voloshchuk I.N. Deported syncytiotrophoblast and placental microparticles in the mother’s body during normal pregnancy and preeclampsia (28 years later). Arkhiv patologii = Archive of Pathology, 2017, Vol. 79, no. 1, pp. 61-67. (In Russ.)]

3. Abalos E., Cuesta C., Grosso A.L., Chou D., Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur. J. Obstet. Gynecol. Reprod. Biol., 2013, Vol. 170, no. 1, pp. 1-7.

4. Abrahams V.M., Kim Y.M., Straszewski S.L., Romero R., Mor G. Macrophages and apoptotic cell clearance during pregnancy. Am. J. Reprod. Immunol., 2004, Vol. 51, no. 4, pp. 275-282.

5. Abrahams V.M., Straszewski-Chavez S.L., Guller S., Mor G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol. Hum. Reprod., 2004, Vol. 10, no. 1, pp. 55-63.

6. Abumaree M.H., Chamley L.W., Badri M., El-Muzaini M.F. Trophoblast debris modulates the expression of immune proteins in macrophages: a key to maternal tolerance of the fetal allograft? J. Reprod. Immunol., 2012, Vol. 94, no. 2, pp. 131-141.

7. Abumaree M.H., Stone P.R., Chamley L.W. The effects of apoptotic, deported human placental trophoblast on macrophages: possible consequences for pregnancy. J. Reprod. Immunol., 2006, Vol. 72, no. 1-2, pp. 33-45.

8. Aharon A., Brenner B., Katz T., Miyagi Y., Lanir N. Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis. Thromb. Haemost., 2004, Vol. 92, no. 4, pp. 776-786.

9. Aharon A., Katzenell S., Tamari T., Brenner B. Microparticles bearing tissue factor and tissue factor pathway inhibitor in gestational vascular complications. J. Thromb. Haemost., 2009, Vol. 7, no. 6, pp. 1047-1050.

10. Alavi A., Axford J.S. The pivotal nature of sugars in normal physiology and disease. Wien Med. Wochenschr., 2006, Vol. 156, no. 1-2, pp. 19-33.

11. Allaire A.D., Ballenger K.A., Wells S.R., McMahon M.J., Lessey B.A. Placental apoptosis in preeclampsia. Obstet. Gynecol., 2000, Vol. 96, no. 2, pp. 271-276.

12. Almeida A., Kolarich D. The promise of protein glycosylation for personalised medicine. Biochim. Biophys. Acta, 2016, Vol. 1860, no. 8, pp. 1583-1595.

13. Aly A.S., Khandelwal M., Zhao J., Mehmet A.H., Sammel M.D., Parry S. Neutrophils are stimulated by syncytiotrophoblast microvillous membranes to generate superoxide radicals in women with preeclampsia. Am. J. Obstet. Gynecol., 2004, Vol. 190, no. 1, pp. 252-258.

14. Amsalem H., Kwan M., Hazan A., Zhang J., Jones R.L., Whittle W., Kingdom J.C., Croy B.A., Lye S.J., Dunk C.E. Identification of a novel neutrophil population: proangiogenic granulocytes in second-trimester human decidua. J. Immunol., 2014, Vol. 193, no. 6, pp. 3070-3079.

15. Ananth C.V., Keyes K.M., Wapner R.J. Pre-eclampsia rates in the United States, 1980-2010: age-periodcohort analysis. BMJ, 2013, Vol. 347, f6564. https://doi.org/10.1136/bmj.f6564.

16. Anderson H.C., Mulhall D., Garimella R. Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis. Lab. Invest., 2010, Vol. 90, no. 11, pp. 1549-1557.

17. Andreu Z., Yanez-Mo M. Tetraspanins in extracellular vesicle formation and function. Front. Immunol., 2014, Vol. 5, p. 442.

18. Apps R., Murphy S.P., Fernando R., Gardner L., Ahad T., Moffett A. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies. Immunology, 2009, Vol. 127, no. 1, pp. 26-39.

19. Arck P.C., Hecher K., Solano M.E. B cells in pregnancy: functional promiscuity or tailored function? Biol. Reprod., 2015, Vol. 92, no. 1, p. 12.

20. Atay S., Gercel-Taylor C., Suttles J., Mor G., Taylor D.D. Trophoblast-derived exosomes mediate monocyte recruitment and differentiation. Am. J. Reprod. Immunol., 2011, Vol. 65, no. 1, pp. 65-77.

21. Atay S., Gercel-Taylor C., Taylor D.D. Human trophoblast-derived exosomal fibronectin induces proinflammatory IL-1beta production by macrophages. Am. J. Reprod. Immunol., 2011, Vol. 66, no. 4, pp. 259-269.

22. Attwood H.D., Park W.W. Embolism to the lungs by trophoblast. J. Obstet. Gynaecol. Br. Commonw., 1961, Vol. 68, no. 4, pp. 611-617.

23. Baig S., Kothandaraman N., Manikandan J., Rong L., Ee K.H., Hill J., Lai C.W., Tan W.Y., Yeoh F., Kale A., Su L.L., Biswas A., Vasoo S., Choolani M. Proteomic analysis of human placental syncytiotrophoblast microvesicles in preeclampsia. Clin. Proteomics, 2014, Vol. 11, no. 1, p. 40.

24. Baig S., Lim J.Y., Fernandis A.Z., Wenk M.R., Kale A., Su L.L., Biswas A., Vasoo S., Shui G., Choolani M. Lipidomic analysis of human placental syncytiotrophoblast microvesicles in adverse pregnancy outcomes. Placenta, 2013, Vol. 34, no. 5, pp. 436-442.

25. Bao Y., Cao X. The immune potential and immunopathology of cytokine-producing B cell subsets: a comprehensive review. J. Autoimmun., 2014, Vol. 55, pp. 10-23.

26. Batista B.S., Eng W.S., Pilobello K.T., Hendricks-Munoz K.D., Mahal L.K. Identification of a conserved glycan signature for microvesicles. J. Proteome Res., 2011, Vol. 10, no. 10, pp. 4624-4633.

27. Biermann M., Maueroder C., Brauner J.M., Chaurio R., Janko C., Herrmann M., Munoz L.E. Surface code - biophysical signals for apoptotic cell clearance. Phys. Biol., 2013, Vol. 10, no. 6, 065007. https://doi.org/10.1088/1478- 3975/10/6/065007.

28. Brinkman van der Linden E.C., Hurtado-Ziola N., Hayakawa T., Wiggleton L., Benirschke K., Varki A., Varki N. Human-specific expression of Siglec-6 in the placenta. Glycobiology, 2007, Vol. 17, no. 9, pp. 922-931.

29. Burton G.J. Deportation of syncytial sprouts from the term human placenta. Placenta, 2011, Vol. 32, no. 1, pp. 96-98.

30. Burton G.J., Fowden A.L. The placenta: a multifaceted, transient organ. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 2015, Vol. 370, no. 1663, 20140066. https://doi.org/10.1098/rstb.2014.0066.

31. Burton G.J., Jones C.J. Syncytial knots, sprouts, apoptosis, and trophoblast deportation from the human placenta. Taiwan J. Obstet. Gynecol., 2009, Vol. 48, no. 1, pp. 28-37.

32. Burton G.J., Woods A.W., Jauniaux E., Kingdom J.C. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta, 2009, Vol. 30, no. 6, pp. 473-482.

33. Burton G.J., Yung H.W. Endoplasmic reticulum stress in the pathogenesis of early-onset pre-eclampsia. Pregnancy Hypertens., 2011, Vol. 1, no. 1-2, pp. 72-78.

34. Caniggia I., Winter J., Lye S.J., Post M. Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia. Placenta, 2000, Vol. 21, Suppl. A, pp. S25-S30.

35. Carosella E.D., Gregori S., LeMaoult J. The tolerogenic interplay(s) among HLA-G, myeloid APCs, and regulatory cells. Blood, 2011, Vol. 118, no. 25, pp. 6499-6505.

36. Chamley L.W., Chen Q., Ding J., Stone P.R., Abumaree M. Trophoblast deportation: just a waste disposal system or antigen sharing? J. Reprod. Immunol., 2011, Vol. 88, no. 2, pp. 99-105.

37. Chen D.B., Wang W. Human placental micrornas and preeclampsia. Biol. Reprod., 2013, Vol. 88, no. 5, p. 130.

38. Chen Q., Chen L., Liu B., Vialli C., Stone P., Ching L.M., Chamley L. The role of autocrine TGFbeta1 in endothelial cell activation induced by phagocytosis of necrotic trophoblasts: a possible role in the pathogenesis of pre-eclampsia. J. Pathol., 2010, Vol. 221, no. 1, pp. 87-95.

39. Chen Q., Guo F., Jin H.Y., Lau S., Stone P., Chamley L. Phagocytosis of apoptotic trophoblastic debris protects endothelial cells against activation. Placenta, 2012, Vol. 33, no. 7, pp. 548-553.

40. Chen Q., Stone P.R., McCowan L.M., Chamley L.W. Phagocytosis of necrotic but not apoptotic trophoblasts induces endothelial cell activation. Hypertension, 2006, Vol. 47, no. 1, pp. 116-121.

41. Chen Y., Huang Y., Jiang R., Teng Y. Syncytiotrophoblast-derived microparticle shedding in early-onset and late-onset severe pre-eclampsia. Int. J. Gynaecol. Obstet., 2012, Vol. 119, no. 3, pp. 234-238.

42. Chua S., Wilkins T., Sargent I., Redman C. Trophoblast deportation in pre-eclamptic pregnancy. Br. J. Obstet. Gynaecol., 1991, Vol. 98, no. 10, pp. 973-979.

43. Cockell A.P., Learmont J.G., Smarason A.K., Redman C.W., Sargent I.L., Poston L. Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function. Br. J. Obstet. Gynaecol., 1997, Vol. 104, no. 2, pp. 235-240.

44. Colombo M., Raposo G., Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol., 2014, Vol. 30, pp. 255-289.

45. Darmochwal-Kolarz D., Leszczynska-Gorzelak B., Rolinski J., Oleszczuk J. The expression and concentrations of Fas/APO-1 (CD95) antigen in patients with severe pre-eclampsia. J. Reprod. Immunol., 2001, Vol. 49, no. 2, pp. 153-164.

46. Darmochwal-Kolarz D., Rolinski J., Leszczynska-Gorzelak B., Oleszczuk J. Fas antigen expression on the decidual lymphocytes of pre-eclamptic patients. Am. J. Reprod. Immunol., 2000, Vol. 43, no. 4, pp. 197-201.

47. Dignat-George F., Camoin-Jau L., Sabatier F., Arnoux D., Anfosso F., Bardin N., Veit V., Combes V., Gentile S., Moal V., Sanmarco M., Sampol J. Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome. Thromb. Haemost., 2004, Vol. 91, no. 4, pp. 667-673.

48. Djurisic S., Hviid T.V. HLA class Ib molecules and immune cells in pregnancy and preeclampsia. Front. Immunol., 2014, Vol. 5, p. 652.

49. Douglas G.W., Thomas L., Carr M., Cullen N.M., Morris R. Trophoblast in the circulating blood during pregnancy. Am. J. Obstet. Gynecol., 1959, Vol. 78, no. 5, pp. 960-973.

50. Dragovic R.A., Collett G.P., Hole P., Ferguson D.J., Redman C.W., Sargent I.L., Tannetta D.S. Isolation of syncytiotrophoblast microvesicles and exosomes and their characterisation by multicolour flow cytometry and fluorescence nanoparticle tracking analysis. Methods, 2015, Vol. 87, pp. 64-74.

51. Dragovic R.A., Southcombe J.H., Tannetta D.S., Redman C.W., Sargent I.L. Multicolor flow cytometry and nanoparticle tracking analysis of extracellular vesicles in the plasma of normal pregnant and pre-eclamptic women. Biol. Reprod., 2013, Vol. 89, no. 6, р. 151.

52. Duckitt K., Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ, 2005, Vol. 330, p. 565.

53. el. Andaloussi S., Mager I., Breakefield X.O., Wood M.J. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov., 2013, Vol. 12, no. 5, pp. 347-357.

54. Escudero C.A., Herlitz K., Troncoso F., Acurio J., Aguayo C., Roberts J.M., Truong G., Duncombe G., Rice G., Salomon C. Role of extracellular vesicles and microRNAs on dysfunctional angiogenesis during preeclamptic pregnancies. Front. Physiol., 2016, Vol. 7, p. 98.

55. Ferreira L.M., Meissner T.B., Tilburgs T., Strominger J.L. HLA-G: at the interface of maternal-fetal tolerance. Trends Immunol., 2017, Vol. 38, no. 4, pp. 272-286.

56. Frangsmyr L., Baranov V., Nagaeva O., Stendahl U., Kjellberg L., Mincheva-Nilsson L. Cytoplasmic microvesicular form of Fas ligand in human early placenta: switching the tissue immune privilege hypothesis from cellular to vesicular level. Mol. Hum. Reprod., 2005, Vol. 11, no. 1, pp. 35-41.

57. Franz S., Herrmann K., Furnrohr B.G., Sheriff A., Frey B., Gaipl U.S., Voll R.E., Kalden J.R., Jack H.M., Herrmann M. After shrinkage apoptotic cells expose internal membrane-derived epitopes on their plasma membranes. Cell Death Differ., 2007, Vol. 14, no. 4, pp. 733-742.

58. Fu G., Brkic J., Hayder H., Peng C. MicroRNAs in human placental development and pregnancy complications. Int. J. Mol. Sci., 2013, Vol. 14, no. 3, pp. 5519-5544.

59. Gardiner C., Tannetta D.S., Simms C.A., Harrison P., Redman C.W., Sargent I.L. Syncytiotrophoblast microvesicles released from pre-eclampsia placentae exhibit increased tissue factor activity. PLoS ONE, 2011, Vol. 6, no. 10, e26313. https://doi.org/10.1371/journal.pone.0026313.

60. Gelber S.E., Brent E., Redecha P., Perino G., Tomlinson S., Davisson R.L., Salmon J.E. Prevention of defective placentation and pregnancy loss by blocking innate immune pathways in a syngeneic model of placental insufficiency. J. Immunol., 2015, Vol. 195, no. 3, pp. 1129-1138.

61. Germain S.J., Sacks G.P., Sooranna S.R., Sargent I.L., Redman C.W. Systemic inflammatory priming in normal pregnancy and preeclampsia: the role of circulating syncytiotrophoblast microparticles. J. Immunol., 2007, Vol. 178, no. 9, pp. 5949-5956.

62. Gilani S.I., Weissgerber T.L., Garovic V.D., Jayachandran M. Preeclampsia and extracellular vesicles. Curr. Hypertens. Rep., 2016, Vol. 18, no. 9, p. 68.

63. Goldman-Wohl D., Yagel S. Preeclampsia - a placenta developmental biology perspective. J. Reprod. Immunol., 2009, Vol. 82, no. 2, pp. 96-99.

64. Gonzalez-Quintero V.H., Smarkusky L.P., Jimenez J.J., Mauro L.M., Jy W., Hortsman L.L., O’Sullivan M.J., Ahn Y.S. Elevated plasma endothelial microparticles: preeclampsia versus gestational hypertension. Am. J. Obstet. Gynecol., 2004, Vol. 191, no. 4, pp. 1418-1424.

65. Goodridge J.P., Burian A., Lee N., Geraghty D.E. HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors. J. Immunol., 2013, Vol. 191, no. 7, pp. 3553-3562.

66. Goswami D., Tannetta D.S., Magee L.A., Fuchisawa A., Redman C.W., Sargent I.L., von Dadelszen P. Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction. Placenta, 2006, Vol. 27, no. 1, pp. 56-61.

67. Gould S.J., Raposo G. As we wait: coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles, 2013, Vol. 2, no. 1, 20389. https://doi.org/10.3402/jev.v2i0.20389.

68. Guller S., Tang Z., Ma Y.Y., Di Santo S., Sager R., Schneider H. Protein composition of microparticles shed from human placenta during placental perfusion: potential role in angiogenesis and fibrinolysis in preeclampsia. Placenta, 2011, Vol. 32, no. 1, pp. 63-69.

69. Gupta A.K., Hasler P., Holzgreve W., Gebhardt S., Hahn S. Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia. Hum. Immunol., 2005, Vol. 66, no. 11, pp. 1146-1154.

70. Gupta A.K., Rusterholz C., Holzgreve W., Hahn S. Syncytiotrophoblast micro-particles do not induce apoptosis in peripheral T lymphocytes, but differ in their activity depending on the mode of preparation. J. Reprod. Immunol., 2005, Vol. 68, no. 1-2, pp. 15-26.

71. Gupta A.K., Rusterholz C., Huppertz B., Malek A., Schneider H., Holzgreve W., Hahn S. A comparative study of the effect of three different syncytiotrophoblast micro-particles preparations on endothelial cells. Placenta, 2005, Vol. 26, no. 1, pp. 59-66.

72. Hackmon R., Pinnaduwage L., Zhang J., Lye S.J., Geraghty D.E., Dunk C.E. Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition. Am. J. Reprod. Immunol., 2017, Vol. 77, no. 6, e12643. https://doi.org/10.1111/aji.12643.

73. Han J., Yang B.P., Li Y.L., Li H.M., Zheng X.H., Yu L.L., Zhang Q., Zheng Y.R., Yi P., Li L., Guo J.X., Zhou Y.G. RhoB/ROCK mediates oxygen-glucose deprivation-stimulated syncytiotrophoblast microparticle shedding in preeclampsia. Cell Tissue Res., 2016, Vol. 366, no. 2, pp. 411-425.

74. He Y.D., Li Y.L., Chen Q. Expression of various subtypes of human leukocyte antigen-G in placenta of patients complicated with severe pre-eclampsia. Zhonghua Fu Chan Ke Za Zhi, 2012, Vol. 47, no. 1, pp. 29-32.

75. Hedlund M., Stenqvist A.C., Nagaeva O., Kjellberg L., Wulff M., Baranov V., Mincheva-Nilsson L. Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: evidence for immunosuppressive function. J. Immunol., 2009, Vol. 183, no. 1, pp. 340-351.

76. Hoegh A.M., Tannetta D., Sargent I., Borup R., Nielsen F.C., Redman C., Sorensen S., Hviid T.V. Effect of syncytiotrophoblast microvillous membrane treatment on gene expression in human umbilical vein endothelial cells. BJOG, 2006, Vol. 113, no. 11, pp. 1270-1279.

77. Holder B.S., Tower C.L., Forbes K., Mulla M.J., Aplin J.D., Abrahams V.M. Immune cell activation by trophoblast-derived microvesicles is mediated by syncytin 1. Immunology, 2012, Vol. 136, no. 2, pp. 184-191.

78. Holder B.S., Tower C.L., Jones C.J., Aplin J.D., Abrahams V.M. Heightened pro-inflammatory effect of preeclamptic placental microvesicles on peripheral blood immune cells in humans. Biol. Reprod., 2012, Vol. 86, no. 4, p. 103.

79. Holland O.J., Linscheid C., Hodes H.C., Nauser T.L., Gilliam M., Stone P., Chamley L.W., Petroff M.G. Minor histocompatibility antigens are expressed in syncytiotrophoblast and trophoblast debris: implications for maternal alloreactivity to the fetus. Am. J. Pathol., 2012, Vol. 180, no. 1, pp. 256-266.

80. Hube F., Reverdiau P., Iochmann S., Trassard S., Thibault G., Gruel Y. Demonstration of a tissue factor pathway inhibitor 2 messenger RNA synthesis by pure villous cytotrophoblast cells isolated from term human placentas. Biol. Reprod., 2003, Vol. 68, no. 5, pp. 1888-1894.

81. Huppertz B., Kadyrov M., Kingdom J.C. Apoptosis and its role in the trophoblast. Am. J. Obstet. Gynecol., 2006, Vol. 195, no. 1, pp. 29-39.

82. Huppertz B., Kingdom J., Caniggia I., Desoye G., Black S., Korr H., Kaufmann P. Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta, 2003, Vol. 24, no. 2-3, pp. 181-190.

83. Ikle F.A. Dissemination of syncytial trophoblastic cells in the maternal blood stream during pregnancy. Bull. Schweiz Akad. Med. Wiss., 1964, Vol. 20, pp. 62-72.

84. Ishitani A., Sageshima N., Lee N., Dorofeeva N., Hatake K., Marquardt H., Geraghty D.E. Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition. J. Immunol., 2003, Vol. 171, no. 3, pp. 1376-1384.

85. Jaameri K.E., Koivuniemi A.P., Carpen E.O. Occurrence of trophoblasts in the blood of toxaemic patients. Gynaecologia, 1965, Vol. 160, no. 5, pp. 315-320.

86. Jauniaux E., Hempstock J., Greenwold N., Burton G.J. Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies. Am. J. Pathol., 2003, Vol. 162, no. 1, pp. 115-125.

87. Jia R., Li J., Rui C., Ji H., Ding H., Lu Y., De W., Sun L. Comparative proteomic profile of the human umbilical cord blood exosomes between normal and preeclampsia pregnancies with high-resolution mass spectrometry. Cell. Physiol. Biochem., 2015, Vol. 36, no. 6, pp. 2299-2306.

88. Johansen M., Redman C.W., Wilkins T., Sargent I.L. Trophoblast deportation in human pregnancy - its relevance for pre-eclampsia. Placenta, 1999, Vol. 20, no. 7, pp. 531-539.

89. Kalra H., Drummen G.P., Mathivanan S. Focus on extracellular vesicles: introducing the next small big thing. Int. J. Mol. Sci., 2016, Vol. 17, no. 2, p. 170.

90. Knight M., Redman C.W., Linton E.A., Sargent I.L. Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol., 1998, Vol. 105, no. 6, pp. 632-640.

91. Kshirsagar S.K., Alam S.M., Jasti S., Hodes H., Nauser T., Gilliam M., Billstrand C., Hunt J.S., Petroff M.G. Immunomodulatory molecules are released from the first trimester and term placenta via exosomes. Placenta, 2012, Vol. 33, no. 12, pp. 982-990.

92. Lacroix R., Plawinski L., Robert S., Doeuvre L., Sabatier F., Martinez de Lizarrondo S., Mezzapesa A., Anfosso F., Leroyer A.S., Poullin P., Jourde N., Njock M.S., Boulanger C.M., Angles-Cano E., Dignat-George F. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis. Haematologica, 2012, Vol. 97, no. 12, pp. 1864-1872.

93. Lavialle C., Cornelis G., Dupressoir A., Esnault C., Heidmann O., Vernochet C., Heidmann T. Paleovirology of ‘syncytins’, retroviral env genes exapted for a role in placentation. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2013, Vol. 368, no. 1626, 20120507. https://doi.org/10.1098/rstb.2012.0507.

94. Lee J.C., Lee K.M., Kim D.W., Heo D.S. Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. J. Immunol., 2004, Vol. 172, no. 12, pp. 7335-7340.

95. Lee X., Keith J.C., Jr., Stumm N., Moutsatsos I., McCoy J.M., Crum C.P., Genest D., Chin D., Ehrenfels C., Pijnenborg R., van Assche F.A., Mi S. Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia. Placenta, 2001, Vol. 22, no. 10, pp. 808-812.

96. le Fevre M.L., U.S. Preventive Services Task Force Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med., 2014, Vol. 161, no. 11, pp. 819-826.

97. Leung D.N., Smith S.C., To K.F., Sahota D.S., Baker P.N. Increased placental apoptosis in pregnancies complicated by preeclampsia. Am. J. Obstet. Gynecol., 2001, Vol. 184, no. 6, pp. 1249-1250.

98. Li H., Han L., Yang Z., Huang W., Zhang X., Gu Y., Li Y., Liu X., Zhou L., Hu J., Yu M., Yang J., Li Y., Zheng Y., Guo J., Han J., Li L. Differential proteomic analysis of syncytiotrophoblast extracellular vesicles from early-onset severe preeclampsia, using 8-plex iTRAQ labeling coupled with 2D nano LC-MS/MS. Cell. Physiol. Biochem., 2015, Vol. 36, no. 3, pp. 1116-1130.

99. Li L., Schust D.J. Isolation, purification and in vitro differentiation of cytotrophoblast cells from human term placenta. Reprod. Biol. Endocrinol., 2015, Vol. 13, p. 71.

100. Liang Y., Eng W.S., Colquhoun D.R., Dinglasan R.R., Graham D.R., Mahal L.K. Complex N-linked glycans serve as a determinant for exosome/microvesicle cargo recruitment. J. Biol. Chem., 2014, Vol. 289, no. 47, pp. 32526-32537.

101. Linscheid C., Heitmann E., Singh P., Wickstrom E., Qiu L., Hodes H., Nauser T., Petroff M.G. Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women. Placenta, 2015, Vol. 36, no. 8, pp. 832-838.

102. Lisonkova S., Joseph K.S. Incidence of preeclampsia: risk factors and outcomes associated with early-versus late-onset disease. Am. J. Obstet. Gynecol., 2013, Vol. 209, no. 6, p. 544.

103. Lo Y.M., Leung T.N., Tein M.S., Sargent I.L., Zhang J., Lau T.K., Haines C.J., Redman C.W. Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia. Clin. Chem., 1999, Vol. 45, no. 2, pp. 184-188.

104. Lok C.A., van der Post J.A., Sargent I.L., Hau C.M., Sturk A., Boer K., Nieuwland R. Changes in microparticle numbers and cellular origin during pregnancy and preeclampsia. Hypertens. Pregnancy, 2008, Vol. 27, no. 4, pp. 344-360.

105. Lokossou A.G., Toudic C., Barbeau B. Implication of human endogenous retrovirus envelope proteins in placental functions. Viruses, 2014, Vol. 6, no. 11, pp. 4609-4627.

106. Lu J., Zhou W.H., Ren L., Zhang Y.Z. CXCR4, CXCR7, and CXCL12 are associated with trophoblastic cells apoptosis and linked to pathophysiology of severe preeclampsia. Exp. Mol. Pathol., 2016, Vol. 100, no. 1, pp. 184-191.

107. Lyons J.J., Milner J.D., Rosenzweig S.D. Glycans instructing immunity: the emerging role of altered glycosylation in clinical immunology. Front. Pediatr., 2015, Vol. 3, p. 54.

108. Macey M.G., Bevan S., Alam S., Verghese L., Agrawal S., Beski S., Thuraisingham R., MacCallum P.K. Platelet activation and endogenous thrombin potential in pre-eclampsia. Thromb. Res., 2010, Vol. 125, no. 3, e76-e81. https://doi.org/10.1016/j.thromres.2009.09.013.

109. Marques F.K., Campos F.M., Filho O.A., Carvalho A.T., Dusse L.M., Gomes K.B. Circulating microparticles in severe preeclampsia. Clin. Chim. Acta, 2012, Vol. 414, pp. 253-258.

110. Meekins J.W., Pijnenborg R., Hanssens M., McFadyen I.R., van Asshe A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol., 1994, Vol. 101, no. 8, pp. 669-674.

111. Meesmann H.M., Fehr E.M., Kierschke S., Herrmann M., Bilyy R., Heyder P., Blank N., Krienke S., Lorenz H.M., Schiller M. Decrease of sialic acid residues as an eat-me signal on the surface of apoptotic lymphocytes. J. Cell. Sci., 2010, Vol. 123, Pt 19, pp. 3347-3356.

112. Messerli M., May K., Hansson S.R., Schneider H., Holzgreve W., Hahn S., Rusterholz C. Feto-maternal interactions in pregnancies: placental microparticles activate peripheral blood monocytes. Placenta, 2010, Vol. 31, no. 2, pp. 106-112.

113. Mikhailova V.A., Ovchinnikova O.M., Zainulina M.S., Sokolov D.I., Selkov S.A. Detection of microparticles of leukocytic origin in the peripheral blood in normal pregnancy and preeclampsia. Bull. Exp. Biol. Med., 2014, Vol. 157, no. 6, pp. 751-756.

114. Mincheva-Nilsson L., Baranov V. Placenta-derived exosomes and syncytiotrophoblast microparticles and their role in human reproduction: immune modulation for pregnancy success. Am. J. Reprod. Immunol., 2014, Vol. 72, no. 5, pp. 440-457.

115. Mincheva-Nilsson L., Baranov V. The role of placental exosomes in reproduction. Am. J. Reprod. Immunol., 2010, Vol. 63, no. 6, pp. 520-533.

116. Mincheva-Nilsson L., Nagaeva O., Chen T., Stendahl U., Antsiferova J., Mogren I., Hernestal J., Baranov V. Placenta-derived soluble MHC class I chain-related molecules down-regulate NKG2D receptor on peripheral blood mononuclear cells during human pregnancy: a possible novel immune escape mechanism for fetal survival. J. Immunol., 2006, Vol. 176, no. 6, pp. 3585-3592.

117. Mitchell M.D., Peiris H.N., Kobayashi M., Koh Y.Q., Duncombe G., Illanes S.E., Rice G.E., Salomon C. Placental exosomes in normal and complicated pregnancy. Am. J. Obstet. Gynecol., 2015, Vol. 213, Suppl. 4, pp. S173-S181.

118. Motta-Mejia C., Kandzija N., Zhang W., Mhlomi V., Cerdeira A.S., Burdujan A., Tannetta D., Dragovic R., Sargent I.L., Redman C.W., Kishore U., Vatish M. Placental vesicles carry active endothelial nitric oxide synthase and their activity is reduced in preeclampsia. Hypertension, 2017, Vol. 70, no. 2, pp. 372-381.

119. Mouillet J.F., Ouyang Y., Coyne C.B., Sadovsky Y. MicroRNAs in placental health and disease. Am. J. Obstet. Gynecol., 2015, Vol. 213, Suppl. 4, pp. S163-S172.

120. Moulin V., Andris F., Thielemans K., Maliszewski C., Urbain J., Moser M. B lymphocytes regulate dendritic cell (DC) function in vivo: increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation. J. Exp. Med., 2000, Vol. 192, no. 4, pp. 475-482.

121. Myatt L., Redman C.W., Staff A.C., Hansson S., Wilson M.L., Laivuori H., Poston L., Roberts J.M.; Global Pregnancy CoLaboratory. Strategy for standardization of preeclampsia research study design. Hypertension, 2014, Vol. 63, no. 6, pp. 1293-1301.

122. Nielsen C.T., Ostergaard O., Johnsen C., Jacobsen S., Heegaard N.H. Distinct features of circulating microparticles and their relationship to clinical manifestations in systemic lupus erythematosus. Arthritis Rheum., 2011, Vol. 63, no. 10, pp. 3067-3077.

123. Orozco A.F., Jorgez C.J., Ramos-Perez W.D., Popek E.J., Yu X., Kozinetz C.A., Bischoff F.Z., Lewis D.E. Placental release of distinct DNA-associated micro-particles into maternal circulation: reflective of gestation time and preeclampsia. Placenta, 2009, Vol. 30, no. 10, pp. 891-897.

124. Ouyang Y., Bayer A., Chu T., Tyurin V.A., Kagan V.E., Morelli A.E., Coyne C.B., Sadovsky Y. Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity. Placenta, 2016, Vol. 47, pp. 86-95.

125. Preston R.A., Jy W., Jimenez J.J., Mauro L.M., Horstman L.L., Valle M., Aime G., Ahn Y.S. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension, 2003, Vol. 41, no. 2, pp. 211-217.

126. Raposo G., Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell. Biol., 2013, Vol. 200, no. 4, pp. 373-383.

127. Reddy A., Zhong X.Y., Rusterholz C., Hahn S., Holzgreve W., Redman C.W., Sargent I.L. The effect of labour and placental separation on the shedding of syncytiotrophoblast microparticles, cell-free DNA and mRNA in normal pregnancy and pre-eclampsia. Placenta, 2008, Vol. 29, no. 11, pp. 942-949.

128. Redman C.W., Sargent I.L. Latest advances in understanding preeclampsia. Science, 2005, Vol. 308, no. 5728, pp. 1592-1594.

129. Redman C.W., Tannetta D.S., Dragovic R.A., Gardiner C., Southcombe J.H., Collett G.P., Sargent I.L. Review: Does size matter? Placental debris and the pathophysiology of pre-eclampsia. Placenta, 2012, Vol. 33, pp. S48-S54.

130. Resic Karara J., Zekic Tomas S., Marusic J., Roje D., Kuzmic Prusac I. Fas and FasL expression in placentas complicated with intrauterine growth retardation with and without preeclampsia. J. Matern. Fetal Neonatal Med., 2016, Vol. 29, no. 7, pp. 1154-1159.

131. Reverdiau P., Jarousseau A.C., Thibault G., Khalfoun B., Watier H., Lebranchu Y., Bardos P., Gruel Y. Tissue factor activity of syncytiotrophoblast plasma membranes and tumoral trophoblast cells in culture. Thromb. Haemost., 1995, Vol. 73, no. 1, pp. 49-54.

132. Roberts J.M., August P.A., Bakris G., Barton J.R., Bernstein I.M., Gaiser R.R., Granger J.P., Jeyabalan A., Johnson D.D., Karumanchi S., Lindheimer M., Owens M.Y., Saade G.R., Sibai B.M., Spong C.Y., Tsigas E., Joseph G.F., O’Reilly N., Politzer A., Son S., Ngaiza K. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet. Gynecol., 2013, Vol. 122, no. 5, pp. 1122-1131.

133. Roberts J.M., Escudero C. The placenta in preeclampsia. Pregnancy Hypertens., 2012, Vol. 2, no. 2, pp. 72-83.

134. Roberts J.M., Lain K.Y. Recent insights into the pathogenesis of pre-eclampsia. Placenta, 2002, Vol. 23, no. 5, pp. 359-372.

135. Roberts J.M., Redman C.W. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet, 1993, Vol. 341, no. 8858, pp. 1447-1451.

136. Sabapatha A., Gercel-Taylor C., Taylor D.D. Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences. Am. J. Reprod. Immunol., 2006, Vol. 56, no. 5-6, pp. 345-355.

137. Sabatier F., Darmon P., Hugel B., Combes V., Sanmarco M., Velut J.G., Arnoux D., Charpiot P., Freyssinet J.M., Oliver C., Sampol J., Dignat-George F. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes, 2002, Vol. 51, no. 9, pp. 2840-2845.

138. Sacks G.P., Studena K., Sargent K., Redman C.W. Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Am. J. Obstet. Gynecol., 1998, Vol. 179, no. 1, pp. 80-86.

139. Salomon C., Guanzon D., Scholz-Romero K., Longo S., Correa P., Illanes S.E., Rice G.E. Placental exosomes as early biomarker of preeclampsia - potential role of exosomal microRNAs across gestation. J. Clin. Endocrinol. Metab., 2017, Vol. 102, no. 9, pp. 3182-3194

140. Salomon C., Kobayashi M., Ashman K., Sobrevia L., Mitchell M.D., Rice G.E. Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS ONE, 2013, Vol. 8, no. 11, e79636. https://doi.org/10.1371/journal. pone.0079636.

141. Salomon C., Rice G.E. Role of exosomes in placental homeostasis and pregnancy disorders. Prog. Mol. Biol. Transl. Sci., 2017, Vol. 145, pp. 163-179.

142. Salomon C., Ryan J., Sobrevia L., Kobayashi M., Ashman K., Mitchell M., Rice G.E. Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis. PLoS ONE, 2013, Vol. 8, no. 7, e68451. https://doi.org/10.1371/journal.pone.0068451.

143. Salomon C., Scholz-Romero K., Sarker S., Sweeney E., Kobayashi M., Correa P., Longo S., Duncombe G., Mitchell M.D., Rice G.E., Illanes S.E. Gestational diabetes mellitus is associated with changes in the concentration and bioactivity of placenta-derived exosomes in maternal circulation across gestation. Diabetes, 2016, Vol. 65, no. 3, pp. 598-609.

144. Salomon C., Torres M.J., Kobayashi M., Scholz-Romero K., Sobrevia L., Dobierzewska A., Illanes S.E., Mitchell M.D., Rice G.E. A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration. PLoS ONE, 2014, Vol. 9, no. 6, e98667. https://doi.org/10.1371/journal.pone.0098667.

145. Sargent I. Microvesicles and pre-eclampsia. Pregnancy Hypertens., 2013, Vol. 3, no. 2, p. 58.

146. Schmidt M., Hoffmann B., Beelen D., Gellhaus A., Winterhager E., Kimmig R., Kasimir-Bauer S. Detection of circulating trophoblast particles in peripheral maternal blood in preeclampsia complicated pregnancies. Hypertens. Pregnancy, 2008, Vol. 27, no. 2, pp. 131-142.

147. Schmorl G. Pathologisch-anatomische untersuchungen über puerperal-eklampsie (pathological and anatomical examinations of puerperal-eclampsia). Leipzig: FCW Vogel, 1893. 106 p.

148. Schneider H. Characterization of extracellular vesicles in plasma of pregnant women using multicolor flow cytometry and nanoparticle tracking analysis. Biol. Reprod., 2013, Vol. 89, no. 6, p. 152.

149. Schrocksnadel H., Daxenbichler G., Artner E., Steckel-Berger G., Dapunt O. Tumor markers in hypertensive disorders of pregnancy. Gynecol. Obstet. Invest., 1993, Vol. 35, no. 4, pp. 204-208.

150. Shen F., Wei J., Snowise S., DeSousa J., Stone P., Viall C., Chen Q., Chamley L. Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: a mechanism by which the placenta communicates with the maternal endothelium. Placenta, 2014, Vol. 35, no. 10, pp. 839-847.

151. Simak J., Gelderman M.P. Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfus. Med. Rev., 2006, Vol. 20, no. 1, pp. 1-26.

152. Smarason A.K., Sargent I.L., Starkey P.M., Redman C.W. The effect of placental syncytiotrophoblast microvillous membranes from normal and pre-eclamptic women on the growth of endothelial cells in vitro. Br. J. Obstet. Gynaecol., 1993, Vol. 100, no. 10, pp. 943-949.

153. Smith N.C., Brush M.G., Luckett S. Preparation of human placental villous surface membrane. Nature, 1974, Vol. 252, no. 5481, pp. 302-303.

154. Sokolov D.I., Ovchinnikova O.M., Korenkov D.A., Viknyanschuk A.N., Benken K.A., Onokhin K.V., Selkov S.A. Influence of peripheral blood microparticles of pregnant women with preeclampsia on the phenotype of monocytes. Transl. Res., 2016, Vol. 170, pp. 112-123.

155. Solier C., Aguerre-Girr M., Lenfant F., Campan A., Berrebi A., Rebmann V., Grosse-Wilde H., Le Bouteiller P. Secretion of pro-apoptotic intron 4-retaining soluble HLA-G1 by human villous trophoblast. Eur. J. Immunol., 2002, Vol. 32, no. 12, pp. 3576-3586.

156. Southcombe J., Tannetta D., Redman C., Sargent I. The immunomodulatory role of syncytiotrophoblast microvesicles. PLoS ONE, 2011, Vol. 6, no. 5, e20245. https://doi.org/10.1371/journal.pone.0020245.

157. Stenqvist A.C., Nagaeva O., Baranov V., Mincheva-Nilsson L. Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosomemediated immune privilege of the fetus. J. Immunol., 2013, Vol. 191, no. 11, pp. 5515-5523.

158. Stepanian A., Bourguignat L., Hennou S., Coupaye M., Hajage D., Salomon L., Alessi M.C., Msika S., de Prost D. Microparticle increase in severe obesity: not related to metabolic syndrome and unchanged after massive weight loss. Obesity (Silver Spring), 2013, Vol. 21, no. 11, pp. 2236-2243.

159. Sukhikh G.T., Ziganshina M.M., Nizyaeva N.V., Kulikova G.V., Volkova J.S., Yarotskaya E.L., Kan N.E., Shchyogolev A.I., Tyutyunnik V.L. Differences of glycocalyx composition in the structural elements of placenta in preeclampsia. Placenta, 2016, Vol. 43, pp. 69-76.

160. Tang Y., Liu H., Li H., Peng T., Gu W., Li X. Hypermethylation of the HLA-G promoter is associated with preeclampsia. Mol. Hum. Reprod., 2015, Vol. 21, no. 9, pp. 736-744.

161. Tannetta D., Collett G., Vatish M., Redman C., Sargent I. Syncytiotrophoblast extracellular vesicles - circulating biopsies reflecting placental health. Placenta, 2017, Vol. 52, pp. 134-138.

162. Tannetta D., Dragovic R., Alyahyaei Z., Southcombe J. Extracellular vesicles and reproduction-promotion of successful pregnancy. Cell. Mol. Immunol., 2014, Vol. 11, no. 6, pp. 548-563.

163. Tannetta D., Mackeen M., Kessler B., Sargent I., Redman C. Multi-dimensional protein identification technology analysis of syncytiotrophoblast vesicles released from perfused preeclampsia placentas. Pregnancy Hypertens., 2012, Vol. 2, no. 3, pp. 201-202.

164. Tannetta D., Masliukaite I., Vatish M., Redman C., Sargent I. Update of syncytiotrophoblast derived extracellular vesicles in normal pregnancy and preeclampsia. J. Reprod. Immunol., 2017, Vol. 119, pp. 98-106.

165. Tannetta D., Sargent I. Placental disease and the maternal syndrome of preeclampsia: missing links? Curr. Hypertens. Rep., 2013, Vol. 15, no. 6, pp. 590-599.

166. Tannetta D.S., Dragovic R.A., Gardiner C., Redman C.W., Sargent I.L. Characterisation of syncytiotrophoblast vesicles in normal pregnancy and pre-eclampsia: expression of Flt-1 and endoglin. PLoS ONE, 2013, Vol. 8, no. 2, e56754. https://doi.org/10.1371/journal.pone.0056754.

167. Tannetta D.S., Hunt K., Jones C.I., Davidson N., Coxon C.H., Ferguson D., Redman C.W., Gibbins J.M., Sargent I.L., Tucker K.L. Syncytiotrophoblast extracellular vesicles from pre-eclampsia placentas differentially affect platelet function. PLoS ONE, 2015, Vol. 10, no. 11, e0142538. https://doi.org/10.1371/journal.pone.0142538.

168. Teng Y., Jiang R., Lin Q., Ding C., Ye Z. The relationship between plasma and placental tissue factor, and tissue factor pathway inhibitors in severe pre-eclampsia patients. Thromb. Res., 2010, Vol. 126, no. 1, e41-e45. https://doi.org/10.1016/j.thromres.2010.02.012.

169. Thibault G., Degenne D., Girard A.C., Guillaumin J.M., Lacord M., Bardos P. The inhibitory effect of human syncytiotrophoblast plasma membrane vesicles on in vitro lymphocyte proliferation is associated with reduced interleukin 2 receptor expression. Cell. Immunol., 1991, Vol. 138, no. 1, pp. 165-174.

170. Tolosa J.M., Schjenken J.E., Clifton V.L., Vargas A., Barbeau B., Lowry P., Maiti K., Smith R. The endogenous retroviral envelope protein syncytin-1 inhibits LPS/PHA-stimulated cytokine responses in human blood and is sorted into placental exosomes. Placenta, 2012, Vol. 33, no. 11, pp. 933-941.

171. Tomas S.Z., Prusac I.K., Roje D., Tadin I. Trophoblast apoptosis in placentas from pregnancies complicated by preeclampsia. Gynecol. Obstet. Invest., 2011, Vol. 71, no. 4, pp. 250-255.

172. Tong M., Chamley L.W. Placental extracellular vesicles and feto-maternal communication. Cold Spring Harb. Perspect. Med., 2015, Vol. 5, no. 3, a023028. https://doi.org/10.1101/cshperspect.a023028.

173. Tramontano A.F., Lyubarova R., Tsiakos J., Palaia T., Deleon J.R., Ragolia L. Circulating endothelial microparticles in diabetes mellitus. Mediators Inflamm., 2010, Vol. 2010, 250476. https://doi.org/10.1155/2010/250476.

174. Vanwijk M.J., Svedas E., Boer K., Nieuwland R., Vanbavel E., Kublickiene K.R. Isolated microparticles, but not whole plasma, from women with preeclampsia impair endothelium-dependent relaxation in isolated myometrial arteries from healthy pregnant women. Am. J. Obstet. Gynecol., 2002, Vol. 187, no. 6, pp. 1686-1693.

175. Vargas A., Zhou S., Ethier-Chiasson M., Flipo D., Lafond J., Gilbert C., Barbeau B. Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia. FASEB J., 2014, Vol. 28, no. 8, pp. 3703-3719.

176. von Dadelszen P., Hurst G., Redman C.W. Supernatants from co-cultured endothelial cells and syncytiotrophoblast microvillous membranes activate peripheral blood leukocytes in vitro. Hum. Reprod., 1999, Vol. 14, no. 4, pp. 919-924.

177. Wei J., Lau S.Y., Blenkiron C., Chen Q., James J.L., Kleffmann T., Wise M., Stone P.R., Chamley L.W. Trophoblastic debris modifies endothelial cell transcriptome in vitro: a mechanism by which fetal cells might control maternal responses to pregnancy. Sci. Rep., 2016, Vol. 6, 30632. https://doi.org/10.1038/srep30632.

178. Yanez-Mo M., Siljander P.R., Andreu Z., Zavec A.B., Borras F.E., Buzas E.I., Buzas K., Casal E., Cappello F., Carvalho J., Colas E., Cordeiro-da Silva A., Fais S., Falcon-Perez J.M., Ghobrial I.M., Giebel B., Gimona M., Graner M., Gursel I., Gursel M., Heegaard N.H., Hendrix A., Kierulf P., Kokubun K., Kosanovic M., Kralj-Iglic V., KramerAlbers E.M., Laitinen S., Lasser C., Lener T., Ligeti E., Line A., Lipps G., Llorente A., Lotvall J., Mancek-Keber M., Marcilla A., Mittelbrunn M., Nazarenko I., Nolte-’t Hoen E.N., Nyman T.A., O’Driscoll L., Olivan M., Oliveira C., Pallinger E., Del Portillo H.A., Reventos J., Rigau M., Rohde E., Sammar M., Sanchez-Madrid F., Santarem N., Schallmoser K., Ostenfeld M.S., Stoorvogel W., Stukelj R., van der Grein S.G., Vasconcelos M.H., Wauben M.H., De Wever O. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles, 2015, Vol. 4, 27066. https://doi.org/10.3402/jev.v4.27066.

179. Zhang X., McGeoch S.C., Johnstone A.M., Holtrop G., Sneddon A.A., MacRury S.M., Megson I.L., Pearson D.W., Abraham P., De Roos B., Lobley G.E., O’Kennedy N. Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status. J. Thromb. Thrombolysis, 2014, Vol. 37, no. 4, pp. 455-463.

180. Zhou Y., Damsky C.H., Chiu K., Roberts J.M., Fisher S.J. Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts. J. Clin. Invest., 1993, Vol. 91, no. 3, pp. 950-960.

181. Zhou Y., Damsky C.H., Fisher S.J. Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? J. Clin. Invest., 1997, Vol. 99, no. 9, pp. 2152-2164.

182. Ziganshina M.M., Pavlovich S.V., Bovin N.V., Sukhikh G.T. Hyaluronic acid in vascular and immune homeostasis during normal pregnancy and preeclampsia. Acta Naturae, 2016, Vol. 8, no. 3, pp. 59-71.