Morphological changes of placental syncytium and their implications for the pathogenesis of preeclampsia

Cellular and Molecular Life Sciences

Volumn 73, Issue 2, 2016, Pages 365-376

  Roland, Cynthia S ^a   Hu, Jian ^c   Ren, Chun E ^d   Chen, Haibin ^e   Li, Jinping ^a,f   Varvoutis, Megan S ^a   Leaphart, Lynn W ^a   Byck, David B ^a   Zhu, Xueqiong ^b   Jiang, Shi Wen ^a,f  

^a MEMORIAL HEALTH UNIVERSITY MEDICAL CENTER   (United States)

^b THE SECOND AFFILIATED HOSPITAL AND YUYING CHILDREN S HOSPITAL OF WENZHOU MEDICAL UNIVERSITY   (China)

^c CHINA PHARMACEUTICAL UNIVERSITY   (China)

^d WEIFANG MEDICAL UNIVERSITY   (China)

^e SHANTOU UNIVERSITY MEDICAL COLLEGE   (China)

^f MERCER UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

HERV W; Nonfusogenic; Preeclampsia; Pregnancy hypertension; Syncytium

Indexed keywords

APOPTOSIS INDUCING FACTOR; CELL PROTEIN; FIBRIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; SYNCYTIN 1; SYNCYTIN 2; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; PLACENTA PROTEIN; SYNCYTIN; VIRUS ENVELOPE PROTEIN;

APOPTOSIS; CELL CYCLE REGULATION; CELL FUSION; CELL LINEAGE; CELL PROLIFERATION; CYTOTROPHOBLAST; DISEASE COURSE; EMBRYO DEVELOPMENT; G1 PHASE CELL CYCLE CHECKPOINT; GENE EXPRESSION; HUMAN; IMMUNOHISTOCHEMISTRY; PATHOGENESIS; PHENOTYPE; PLACENTA; PREECLAMPSIA; PROTEIN EXPRESSION; PROTEIN FUNCTION; REPERFUSION INJURY; REVIEW; SYNCYTIOTROPHOBLAST; SYNCYTIUM; TROPHOBLAST; ANIMAL; CYTOLOGY; FEMALE; GIANT CELL; METABOLISM; PATHOLOGY; PREGNANCY;

ANIMALS; APOPTOSIS; CELL FUSION; CELL PROLIFERATION; FEMALE; GENE PRODUCTS, ENV; GIANT CELLS; HUMANS; PLACENTA; PRE-ECLAMPSIA; PREGNANCY; PREGNANCY PROTEINS; TROPHOBLASTS;

EID: 84953896574     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-015-2069-x     Document Type: Review

References (77)

1. Hypertension in Pregnancy (2013) Task force on hypertension in pregnancy. American College of Obstetricians and Gynecologists. http://www.acog.org/-/media/Task-Force-and-Work-Group-Reports/HypertensioninPregnancy.pdf?dmc=1. Accessed Jan 2015
2. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PFA (2009) The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ 88:31-38
3. Mercuro G, Bassareo PP, Flore G, Fanos V, Dentamaro I, Scicchitano P, Laforgia N, Ciccone MM (2013) Prematurity and low weight at birth as new conditions predisposing to an increased cardiovascular risk. Eur J Prev Cardiol 20(2):357-367
4. Moster D, Lie RT, Markstad T (2008) Long-term medical and social consequences of preterm birth. N Engl J Med 359(3):262-273
5. Enguobahrie D, Abetwe D, Sorensen T, Willoughby D, Chidambaram K, Williams M (2011) Placental microRNA expression in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 204:178.2-178.21
6. Gauster M, Moser G, Orendi K, Huppertz B (2009) Factors involved in regulating trophoblast fusion: potential role in the development of preeclampsia. Placenta 23:49-54
7. Redman CWG, Sargent IL (2008) Circulating microparticles in normal pregnancy and pre-eclampsia. Placenta 29:73-77
8. Gauster M, Huppertz B (2008) Fusion of cytotrophoblast with syncytiotrophoblast in the human placenta: factors involved in syncytialization. J Reprod Med Endocrinol 5:76-82
9. Dokras A, Hoffmann D, Eaastvold J, Kienzle M, Gruman L, Kirby P, Weiss R, Davisson R (2006) Severe feto-placental abnormalities precede the onset of hypertension and proteinuria in a mouse model of preeclampsia. Biol Reprod 75(6):899-907
10. Cross J (2000) Genetic insights into trophoblast differentiation and placental morphogenesis. Semin Cell Dev Biol 11(2):105-113
11. Newhouse S, Davidge S, Winkler-Lowen B, Demianczuk N, Guklbert L (2007) In vitro differentiation of villous trophoblasts from pregnancies complicated by intrauterine growth restriction with and without preeclampsia. Placenta 28(10):999-1003
12. Brouillet S, Hoffmann P, Feige JJ, Alfaidy N (2012) EG-VEGF: a key endocrine factor in placental development. Trends Endocrinol Metab 23(10):501-508
13. Maynard SE, Karumanchi SA (2011) Angiogenic factors and preeclampsia. Semin Nephrol 31(1):33-46
14. Stepan H, Unversucht A, Wessel N, Faber R (2007) Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion. Hypertension 49(4):818-824
15. Mayhew TM (2014) Turnover of human villous trophoblast in normal pregnancy: what do we know and what do we need to know? Placenta 35(4):229-240
16. Huang Q, Li J, Wang F, Oliver MT, Tipton T, Gao Y, Jiang SW (2013) Syncytin-1 modulates placental trophoblast cell proliferation by promoting G1/S transition. Cell Signal 25(4):1027-1035
17. Mayhew TM, Manwani R, Ohadike C, Wijeskara J, Baker PN (2007) The placenta in pre-eclampsia and intrauterine growth restriction: studies on exchange surface areas, diffusion distances and villous membrane diffusive conductances. Placenta 28(2-3):233-238
18. Redline RW, Patterson P (1995) Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. Hum Pathol 26(6):594-600
19. Vatgas A, Toufaily C, LeBellego F, Rassart E, Lafond J, Barbeau B (2011) Reduced expression of both syncytin 1 and syncytin 2 correlates with severity of preeclampsia. Reprod Sci 18(11):1085-1091
20. Ruebner M, Strissel PL, Ekici AB, Stiegler E, Dammer U, Goecke TW, Faschingbauer F, Fahlbusch FB, Beckmann MW, Strick R (2013) Reduced syncytin-1 expression levels in placental syndromes correlates with epigenetic hypermethylation of the ERVW-1 promotor region. PLoS One 8:e56145
21. Zhuang XW, Li J, Brost BC, Xia XY, Chen HB, Wang CX, Jiang SW (2014) Decreased expression and altered methylation of syncytin-1 gene in human placentas associated with preeclampsia. Curr Pharm Des 20(11):1796-1802
22. Gao Y, He Z, Wang Z, Luo Y, Sun H, Zhou Y, Huang L, Li M, Fang Q, Jiang S (2012) Increased expression and altered methylation of HERVWE1 in the human placentas of smaller fetuses from monozygotic, dichorionic, discordant twins. PLoS One 7:e33503
23. Gong JS, Kim GJ (2014) The role of autophagy in the placenta as a regulator of cell death. Clin Exp Reprod Med 41(3):97-107
24. Oh SY, Choi SJ, Kim KH, Cho EY, Kim JH, Roh CR (2008) Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia. Reprod Sci 15(9):912-920
25. Hung TH, Chen SF, Lo LM, Li MJ, Yeh YL, Hsieh TT (2012) Increased autophagy in placentas of intrauterine growth-restricted pregnancies. PLoS One 7:e40957
26. Chen B, Longtine SM, Nelson DM (2012) Hypoxia induces autophagy in primary human trophoblasts. Endocrinology 153(10):4946-4954
27. Cha HH, Hwang JR, Kim HY, Choi SJ, Oh SY, Roh CR (2014) Autophagy induced by tumor necrosis factor a mediates intrinsic apoptosis in trophoblastic cells. Reprod Sci 21(5):612-622
28. Asklund K, Chamley L (2011) Trophoblast deportation part I: review of the evidence demonstrating trophoblast shedding and deportation during human pregnancy. Placenta 32(10):716-723
29. Douglas GW, Thomas L, Carr M, Cullen NM, Morris R (1959) Trophoblast in the circulating blood during pregnancy. Am J Obstet Gynecol 78:960-973
30. Schmidt M, Hoffman B, Beelen D, Gellhaus A, Winterhager E, Kimming R (2008) Detection of circulating trophoblast particles in peripheral maternal blood in preeclampsia complicated pregnancies. Hypertens Pregnancy 27(2):131-142
31. Heazell AE, Moll SJ, Jones CJ, Baker PN, Crocker IP (2007) Formation of syncytial knots is increased by hyperoxia, hypoxia and reactive oxygen species. Placenta 28:33-40
32. Austgulen R, Isaksen C, Chedwick L, Romundstad P, Vatten L, Craven C (2004) Preeclampsia: associated with increased syncytial apoptosis when the infant is small-for-gestational-age. J Reprod Immunol 61(1):39-50
33. Rajakumar A, Cerdeira AS, Rana S, Zsengeller Z, Edmunds L, Jeyabalan A, Hubel CA, Stillman IE, Parikh SM, Karumanchi SA (2012) Transcriptionally active syncytial aggregates in the maternal circulation may contribute to circulating soluble fms-like tyrosine kinase 1 in preeclampsia. Hypertension 59(2):256-264
34. Chamley LW, Chen Q, Ding J, Stone PR, Abumaree M (2011) Trophoblast deportation: just a waste disposal system or antigen sharing? J Reprod Immunol 88(2):99-105
35. Pantham P, Askelund KJ, Chamley LW (2011) Trophoblast deportation part II: a review of the maternal consequences of trophoblast deportation. Placenta 32(10):724-731
36. Huppertz B (2010) IFPA award in placentology lecture: biology of the placental syncytiotrophoblast - myths and facts. Placenta 31:75-81
37. Lockwood CJ, Huang SJ, Krikun G, Caze R, Rahman M, Buchwalder LF, Schatz F (2011) Decidual hemostasis, inflammation and angiogenesis in pre-eclampsia. Semin Thromb Hemost 37(2):158-164
38. Staff AC, Johnsen GM, Dechend R, Redman CW (2014) Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors. J Reprod Immunol 101-102:120-126
39. Burton GJ, Jones CJ (2009) Syncytial knots, sprouts, apoptosis, and trophoblast deportation from the human placenta. Taiwan J Obstet Gynecol 48(1):28-37
40. Loukeris K, Sela R, Baergen RN (2010) Syncytial knots as a reflection of placental maturity: reference values for 20 to 40 weeks' gestational age. Pediatr Dev Pathol 13(4):305-309
41. Benirschke K (1998) Remarkable placenta. Clin Anat 11(3):194-205
42. Fogarty NM, Ferguson-Smith AC, Burton GJ (2013) Syncytial knots (Tenney-Parker changes) in the human placenta: evidence of loss of transcriptional activity and oxidative damage. Am J Pathol 183(1):144-152
43. Stark M, Clark L, Craver R (2014) Histologic differences in placentas of preeclamptic/eclamptic gestations by birthweight, placental weight, and time of onset. Pediatr Dev Pathol 17(3):181-189
44. Devisme L, Merlot B, Ego A, Houfflin-Debarge V, Deruelle P, Subtil D (2013) A case-control study of placental lesions associated with pre-eclampsia. Int J Gynaecol Obstet 120(2):165-168
45. Salgado S, Salgado M (2011) Structural changes in pre-eclamptic and eclamptic placentas - an ultrastructural study. J Coll Physicians Surg Pak 21(8):482-486
46. Coleman SJ, Gerza L, Jones CJ, Sibley CP, Aplin JD, Heazell AE (2013) Syncytial nuclear aggregates in normal placenta show increased nuclear condensation, but apoptosis and cytoskeletal redistribution are uncommon. Placenta 34(5):449-455
47. Huang Q, Chen H, Wang F, Brost BC, Li J, Gao Y, Li Z, Gao Y, Jiang SW (2014) Reduced syncytin-1 expression in choriocarcinoma BeWo cells activates the calpain1-AIF-mediated apoptosis, implication for preeclampsia. Cell Mol Life Sci 71(16):3151-3165
48. Hwang HS, Sohn IS, Kwon HS (2012) The clinical significance of large placental lakes. Eur J Obstet Gynecol Reprod Biol 162(2):139-143
49. Petersen OMF, Heller D, Joshi V (2006) Handbook of placental pathology. Taylor & Francis, Oxford
50. Hung TH, Skepper JN, Charnock-Jones DS, Burton GJ (2002) Hypoxia-reoxygenation: a potent inducer of apoptotic changes in the human placenta and possible etiological factor in preeclampsia. Circ Res 90(12):1274-1281
51. Guller S (2009) Role of the syncytium in placenta-mediated complications of preeclampsia. Thromb Res 124(4):389-392
52. Narasimah A, Vasudeva DS (2011) Spectrum of changes in placenta in toxemia of pregnancy. Indian J Pathol Microbiol 54(1):15-20
53. Hladunewich M, Karumanchi SA, Lafayette R (2007) Pathophysiology of the clinical manifestations of preeclampsia. Clin J Am Soc Nephrol 2(3):543-549
54. Khong TY, De Wolf F, Robertson WB, Brosens I (1986) Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol 93(10):1049-1059
55. Tenney B, Parker F (1940) The placenta in toxemia of pregnancy. Am J Obstet Gynecol 39(6):1000-1005
56. Sankar KD, Bhanu PS, Kiran S, Ramakrishna BA, Shanthi V (2012) Vasculosyncytial membrane in relation to syncytial knots complicates the placenta in preeclampsia: a histomorphometrical study. Anat Cell Biol 45(2):86-91
57. Sodhi S, Mohan H, Jaiswal TS, Mohan PS, Rathee S (1990) Placental pathology in preeclampsia eclampsia syndrome. Indian J Pathol Microbiol 33(1):11-16
58. Soma H, Yoshida K, Mukaida T, Tabuchi Y (1982) Morphologic changes in the hypertensive placenta. Contrib Gynecol Obstet 9:58-75
59. Ishihara N, Matsuo H, Murakoshi H, Laoag-Fernandez JB, Samoto T, Mauruo T (2002) Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gyncecol 186(1):158-166
60. Jones CJ, Fox H (1980) An ultrastructural and ultrahistochemical study of the human placenta in maternal pre-eclampsia. Placenta 1(1):61-76
61. MacLennan AH, Sharp F, Shaw-Dunn J (1972) The ultrastructure of human trophoblast in spontaneous and induced hypoxia using a system of organ culture. J Obstet Gynaecol Br Commonw 79(2):113-121
62. Huang Q, Chen H, Li J, Oliver M, Ma X, Byck D, Gao Y, Jiang S (2013) Epigenetic and non-epigenetic regulation of syncytin-1 expression in human placenta and carrier tissues. Cell Signal 26(3):648-656
63. Langbein M, Strick R, Strissel PL, Vogt N, Parsch H, Beckman MW, Schild RL (2008) Impaired cytotrophoblast cell-cell fusion is associated with reduced syncytin and increased apoptosis in patients with placental dysfunction. Mol Reprod Dev 75(1):175-183
64. Matouskova M, Blazkova J, Pajer P, Pavlicek A, Hejnar J (2006) CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues. Exp Cell Res 312(7):1011-1020
65. Lee X, Keith JC Jr, Stumm N, Moutsatsos I, McCoy JM, Crum CP, Genest D, Chin D, Ehrenfels C, Pijnenborg R, van Assche FA, Mi S (2001) Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia. Placenta 22(10):808-812
66. Arnholdt H, Meisel F, Fandrey K, Lohrs U (1991) Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies. Virch Arch B Cell Pathol Incl Mol Pathol 60(6):365-372
67. Knerr I, Weigel C, Linnemann K, Dötsch J, Meissner U, Fusch C, Rascher W (2003) Transcriptional effects of hypoxia on fusiogenic syncytin and its receptor ASCT2 in human cytotrophoblast BeWo cells and in ex vivo perfused placental cotyledons. Am J Obstet Gynecol 189(2):583-588
68. Tolosa JM, Schjenken JE, Clifton VL, Vargas A, Barbeau B, Lowry P, Maiti K, Smith R (2012) The endogenous retroviral envelope protein syncytin-1 inhibits LPS/PHA-stimulated cytokine responses in human blood and is sorted into placental exosomes. Placenta 33(11):933-941
69. Gilabert J, Estellés A, Grancha S, España F, Aznar J (1995) Fibrinolytic system and reproductive process with special reference to fibrinolytic failure in pre-eclampsia. Hum Reprod 10:121-131
70. Kanfer A, Bruch JF, Nguyen G, He CJ, Delarue F, Flahault A, Nessmann C, Uzan S (1996) Increased placental antifibrinolytic potential and fibrin deposits in pregnancy-induced hypertension and preeclampsia. Lab Invest 74(1):253-258
71. Tanjung MT, Siddik HD, Hariman H, Koh SC (2005) Coagulation and fibrinolysis in preeclampsia and neonates. Clin Appl Thromob Hemost 11(4):467-473
72. Pinheiro MB, Gomes KB, Dusse LM (2013) Fibrinolytic system in preeclampsia. Clin Chim Acta 416:67-71
73. Guller S, Yula YM, Han-Hsuan F, Krikun G, Abrahams VM, Mor G (2008) The placental syncytium and the pathophysiology of preeclampsia and intrauterine growth restriction: a novel assay to assess syncytial protein expression. Ann N Y Acad Sci 1127:129-133
74. Arkwright PD, Rademacher TW, Dwek RA, Redman CW (1993) Preeclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles. J Clin Investig 91(6):2744-2753
75. Salge AK, Rocha KM, Xavier RM, Ramalho WS, Rocha ÉL, Guimarães JV, Silva RC, Siqueira KM, Abdalla DR, Michelin MA, Murta EF (2012) Macroscopic placental changes associated with fetal and maternal events in diabetes mellitus. Clinics (Sao Paulo) 67(10):1203-1208
76. Nahar L, Nahar K, Hossain MI, Yasmin H, Annur BM (2015) Placental changes in pregnancy induced hypertension and its impacts on fetal outcome. Mymensingh Med J 24(1):9-17
77. Chen KH, Chen LR, Lee YH (2011) Exploring the relationship between preterm placental calcification and adverse maternal and fetal outcome. Ultrasound Obstet Gynecol 37(3):328-334