Placenta
Volume 29, Issue 9 , Pages 772-783 , September 2008

Live and Let Die – Regulation of Villous Trophoblast Apoptosis in Normal and Abnormal Pregnancies

,Accepted 3 July 2008.

References 

  1. Levy R, Nelson DM. To be, or not to be, that is the question. Apoptosis in human trophoblast. Placenta. 2000;21(1):1–13
  2. Wong SY, Ngan HY, Chan CC, Cheung AN. Apoptosis in gestational trophoblastic disease is correlated with clinical outcome and Bcl-2 expression but not Bax expression. Mod Pathol. 1999;12(11):1025–1033
  3. Chiu PM, Ngan YS, Khoo US, Cheung AN. Apoptotic activity in gestational trophoblastic disease correlates with clinical outcome: assessment by the caspase-related M30 CytoDeath antibody. Histopathology. 2001;38(3):243–249
  4. Allaire AD, Ballenger KA, Wells SR, McMahon MJ, Lessey BA. Placental apoptosis in preeclampsia. Obstet Gynecol. 2000;96(2):271–276
  5. Leung DN, Smith SC, To KF, Sahota DS, Baker PN. Increased placental apoptosis in pregnancies complicated by preeclampsia. Am J Obstet Gynecol. 2001;184(6):1249–1250
  6. Endo H, Okamoto A, Yamada K, Nikaido T, Tanaka T. Frequent apoptosis in placental villi from pregnancies complicated with intrauterine growth restriction and without maternal symptoms. Int J Mol Med. 2005;16(1):79–84
  7. Levy R, Smith SD, Yusuf K, Huettner PC, Kraus FT, Sadovsky Y, et al. Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression. Am J Obstet Gynecol. 2002;186(5):1056–1061
  8. Huppertz B, Frank HG, Reister F, Kingdom J, Korr H, Kaufmann P. Apoptosis cascade progresses during turnover of human trophoblast: analysis of villous cytotrophoblast and syncytial fragments in vitro. Lab Invest. 1999;79(12):1687–1702
  9. Nasmyth K. Viewpoint: putting the cell cycle in order. Science. 1996;274(5293):1643–1645
  10. Lees E. Cyclin dependent kinase regulation. Curr Opin Cell Biol. 1995;7(6):773–780
  11. Pardee AB. G1 events and regulation of cell proliferation. Science. 1989;246(4930):603–608
  12. Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995;9(10):1149–1163
  13. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239–257
  14. Lazebnik YA, Cole S, Cooke CA, Nelson WG, Earnshaw WC. Nuclear events of apoptosis in vitro in cell-free mitotic extracts: a model system for analysis of the active phase of apoptosis. J Cell Biol. 1993;123(1):7–22
  15. Arends MJ, Wyllie AH. Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol. 1991;32:223–254
  16. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148(7):2207–2216
  17. Edinger AL, Thompson CB. Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 2004;16(6):663–669
  18. Fadeel B, Orrenius S. Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med. 2005;258(6):479–517
  19. Nunez G, Benedict MA, Hu Y, Inohara N. Caspases: the proteases of the apoptotic pathway. Oncogene. 1998;17(25):3237–3245
  20. Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, et al. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell. 1998;94(3):325–337
  21. Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, et al. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death—inducing signaling complex. Cell. 1996;85(6):817–827
  22. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature. 1998;391(6662):43–50
  23. Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol. 2001;3(4):339–345
  24. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, et al. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol. 1999;144(2):281–292
  25. Slee EA, Adrain C, Martin SJ. Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. J Biol Chem. 2001;276(10):7320–7326Epub 2000 Oct 31
  26. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 1998;94(4):481–490
  27. Nicholson DW, Thornberry NA. Apoptosis. Life and death decisions. Science. 2003;299(5604):214–215
  28. Dhein J, Walczak H, Baumler C, Debatin KM, Krammer PH. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature. 1995;373(6513):438–441
  29. Zheng L, Fisher G, Miller RE, Peschon J, Lynch DH, Lenardo MJ. Induction of apoptosis in mature T cells by tumour necrosis factor. Nature. 1995;377(6547):348–351
  30. Hsu H, Xiong J, Goeddel DV. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell. 1995;81(4):495–504
  31. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A. Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 2000;12(6):611–620
  32. Yui J, Garcia-Lloret M, Wegmann TG, Guilbert LJ. Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts. Placenta. 1994;15(8):819–835
  33. Woo RA, McLure KG, Lees-Miller SP, Rancourt DE, Lee PW. DNA-dependent protein kinase acts upstream of p53 in response to DNA damage. Nature. 1998;394(6694):700–704
  34. Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis – the p53 network. J Cell Sci. 2003;116(Pt 20):4077–4085
  35. Finch RA, Donoviel DB, Potter D, Shi M, Fan A, Freed DD, et al. mdmx is a negative regulator of p53 activity in vivo. Cancer Res. 2002;62(11):3221–3225
  36. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature. 1997;387(6630):296–299
  37. Lu W, Pochampally R, Chen L, Traidej M, Wang Y, Chen J. Nuclear exclusion of p53 in a subset of tumors requires MDM2 function. Oncogene. 2000;19(2):232–240
  38. Tsujimoto Y, Croce CM. Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A. 1986;83(14):5214–5218
  39. Huang DC, Adams JM, Cory S. The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4. EMBO J. 1998;17(4):1029–1039
  40. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P. Toxic proteins released from mitochondria in cell death. Oncogene. 2004;23(16):2861–2874
  41. Donovan M, Cotter TG. Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death. Biochim Biophys Acta. 2004;1644(2–3):133–147
  42. Schendel SL, Xie Z, Montal MO, Matsuyama S, Montal M, Reed JC. Channel formation by antiapoptotic protein Bcl-2. Proc Natl Acad Sci U S A. 1997;94(10):5113–5118
  43. Shimizu S, Narita M, Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 1999;399(6735):483–487
  44. Beham A, Marin MC, Fernandez A, Herrmann J, Brisbay S, Tari AM, et al. Bcl-2 inhibits p53 nuclear import following DNA damage. Oncogene. 1997;15(23):2767–2772
  45. Holcik M, Gibson H, Korneluk RG. XIAP: apoptotic brake and promising therapeutic target. Apoptosis. 2001;6(4):253–261
  46. Wheatley SP, McNeish IA. Survivin: a protein with dual roles in mitosis and apoptosis. Int Rev Cytol. 2005;247:35–88
  47. Davoodi J, Lin L, Kelly J, Liston P, MacKenzie AE. Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9. J Biol Chem. 2004;279(39):40622–40628[Epub 2004 Jul 26]
  48. Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell. 2000;102(1):43–53
  49. Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 2000;102(1):33–42
  50. de Rozieres S, Maya R, Oren M, Lozano G. The loss of mdm2 induces p53-mediated apoptosis. Oncogene. 2000;19(13):1691–1697
  51. Sorenson CM. Bcl-2 family members and disease. Biochim Biophys Acta. 2004;1644(2–3):169–177
  52. Jones SN, Roe AE, Donehower LA, Bradley A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature. 1995;378(6553):206–208
  53. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA, Butel JS, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992;356(6366):215–221
  54. Jones CJ, Fox H. Ultrastructure of the normal human placenta. Electron Microsc Rev. 1991;4:129–178
  55. Huppertz B, Kingdom JC. Apoptosis in the trophoblast—role of apoptosis in placental morphogenesis. J Soc Gynecol Investig. 2004;11(6):353–362
  56. Johansen M, Redman CW, Wilkins T, Sargent IL. Trophoblast deportation in human pregnancy—its relevance for pre-eclampsia. Placenta. 1999;20(7):531–539
  57. Black S, Kadyrov M, Kaufmann P, Ugele B, Emans N, Huppertz B. Syncytial fusion of human trophoblast depends on caspase 8. Cell Death Differ. 2004;11(1):90–98
  58. Yusuf K, Smith SD, Sadovsky Y, Nelson DM. Trophoblast differentiation modulates the activity of caspases in primary cultures of term human trophoblasts. Pediatr Res. 2002;52(3):411–415
  59. Kadyrov M, Kaufmann P, Huppertz B. Expression of a cytokeratin 18 neo-epitope is a specific marker for trophoblast apoptosis in human placenta. Placenta. 2001;22(1):44–48
  60. Smith SC, Baker PN, Symonds EM. Placental apoptosis in normal human pregnancy. Am J Obstet Gynecol. 1997;177(1):57–65
  61. Burton GJ, Skepper JN, Hempstock J, Cindrova T, Jones CJ, Jauniaux E. A reappraisal of the contrasting morphological appearances of villous cytotrophoblast cells during early human pregnancy; evidence for both apoptosis and primary necrosis. Placenta. 2003;24(4):297–305
  62. Jones CJ, Fox H. Syncytial knots and intervillous bridges in the human placenta: an ultrastructural study. J Anat. 1977;124(2):275–286
  63. Jones CJ, Fox H. An ultrastructural and ultrahistochemical study of the human placenta in maternal pre-eclampsia. Placenta. 1980;1(1):61–76
  64. Smith SC, Baker PN. Placental apoptosis is increased in post-term pregnancies. Br J Obstet Gynaecol. 1999;106(8):861–862
  65. Athapathu H, Jayawardana MA, Senanayaka L. A study of the incidence of apoptosis in the human placental cells in the last weeks of pregnancy. J Obstet Gynaecol. 2003;23(5):515–517
  66. Jauniaux E, Hempstock J, Greenwold N, Burton GJ. 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;162(1):115–125
  67. Kale A, Soylemez F, Ensari A. Expressions of proliferation markers (Ki-67, proliferating cell nuclear antigen, and silver-staining nucleolar organizer regions) and of p53 tumor protein in gestational trophoblastic disease. Am J Obstet Gynecol. 2001;184(4):567–574
  68. Hempstock J, Jauniaux E, Greenwold N, Burton GJ. The contribution of placental oxidative stress to early pregnancy failure. Hum Pathol. 2003;34(12):1265–1275
  69. Ishihara N, Matsuo H, Murakoshi H, Laoag-Fernandez JB, Samoto T, Maruo T. Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gynecol. 2002;186(1):158–166
  70. Smith SC, Baker PN, Symonds EM. Increased placental apoptosis in intrauterine growth restriction. Am J Obstet Gynecol. 1997;177(6):1395–1401
  71. Ratts VS, Tao XJ, Webster CB, Swanson PE, Smith SD, Brownbill P, et al. Expression of BCL-2, BAX and BAK in the trophoblast layer of the term human placenta: a unique model of apoptosis within a syncytium. Placenta. 2000;21(4):361–366
  72. Tenney B, Parker F. The placenta in toxaemia of pregnancy. Am J Obstet Gynecol. 1940;39:1000–1005
  73. Heazell AE, Moll SJ, Jones CJ, Baker PN, Crocker IP. Formation of syncytial knots is increased by hyperoxia, hypoxia and reactive oxygen species. Placenta. 2007;28(Suppl 1):S33–S40
  74. Crocker IP, Tansinda DM, Baker PN. Altered cell kinetics in cultured placental villous explants in pregnancies complicated by pre-eclampsia and intrauterine growth restriction. J Pathol. 2004;204(1):11–18
  75. Crocker IP, Cooper S, Ong SC, Baker PN. Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am J Pathol. 2003;162(2):637–643
  76. Kharfi A, Bureau M, Giguere Y, Moutquin JM, Forest JC. Dissociation between increased apoptosis and expression of the tumor necrosis factor-alpha system in term placental villi with preeclampsia. Clin Biochem. 2006;39(6):646–651[Epub 2006 Feb 23]
  77. De Falco M, Fedele V, Cobellis L, Mastrogiacomo A, Leone S, Giraldi D, et al. Immunohistochemical distribution of proteins belonging to the receptor-mediated and the mitochondrial apoptotic pathways in human placenta during gestation. Cell Tissue Res. 2004;318(3):599–608
  78. Pongcharoen S, Searle RF, Bulmer JN. Placental Fas and Fas ligand expression in normal early, term and molar pregnancy. Placenta. 2004;25(4):321–330
  79. Abrahams VM, Straszewski-Chavez SL, Guller S, Mor G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod. 2004;10(1):55–63
  80. Kilani RT, Mackova M, Davidge ST, Winkler-Lowen B, Demianczuk N, Guilbert LJ. Endogenous tumor necrosis factor alpha mediates enhanced apoptosis of cultured villous trophoblasts from intrauterine growth-restricted placentae. Reproduction. 2007;133(1):257–264
  81. Marzusch K, Ruck P, Horny H-P, Dietl J, Kaiserling E. Expression of the p53 tumour suppressor gene in human placenta: an immunohistochemical study. Placenta. 1995;16:101–114
  82. Roncalli M, Bulfamante G, Viale G, Springall DR, Alfano R, Comi A, et al. C-myc and tumour suppressor gene product expression in developing and term human trophoblast. Placenta. 1994;15(4):399–409
  83. Sakuragi N, Matsuo H, Coukos G, Furth EE, Bronner MP, VanArsdale CM, et al. Differentiation-dependent expression of the BCL-2 proto-oncogene in the human trophoblast lineage. J Soc Gynecol Investig. 1994;1(2):164–172
  84. Quenby S, Brazeau C, Drakeley A, Lewis-Jones DI, Vince G. Oncogene and tumour suppressor gene products during trophoblast differentiation in the first trimester. Mol Hum Reprod. 1998;4(5):477–481
  85. Haidacher S, Blaschitz A, Desoye G, Dohr G. Immunohistochemical evidence of p53 protein in human placenta and choriocarcinoma cell lines. Hum Reprod. 1995;10(4):983–988
  86. Shi YF, Xie X, Zhao CL, Ye DF, Lu SM, Hor JJ, et al. Lack of mutation in tumour-suppressor gene p53 in gestational trophoblastic tumours. Br J Cancer. 1996;73(10):1216–1219
  87. Cheung AN, Shen DH, Khoo US, Chiu MP, Tin VP, Chung LP, et al. Immunohistochemical and mutational analysis of p53 tumor suppressor gene in gestational trophoblastic disease: correlation with mdm2, proliferation index, and clinicopathologic parameters. Int J Gynecol Cancer. 1999;9(2):123–130
  88. Fulop V, Mok SC, Genest DR, Gati I, Doszpod J, Berkowitz RS. p53, p21, Rb and mdm2 oncoproteins. Expression in normal placenta, partial and complete mole, and choriocarcinoma. J Reprod Med. 1998;43(2):119–127
  89. Heazell AE, Lacey HA, Jones CJ, Huppertz B, Baker PN, Crocker IP. Effects of oxygen on cell turnover and expression of regulators of apoptosis in human placental trophoblast. Placenta. 2008;29(2):175–186
  90. Toki T, Horiuchi A, Ichikawa N, Mori A, Nikaido T, Fujii S. Inverse relationship between apoptosis and Bcl-2 expression in syncytiotrophoblast and fibrin-type fibrinoid in early gestation. Mol Hum Reprod. 1999;5(3):246–251
  91. De Falco M, Cobellis L, Giraldi D, Mastrogiacomo A, Perna A, Colacurci N, et al. Expression and distribution of notch protein members in human placenta throughout pregnancy. Placenta. 2007;28(2–3):118–126
  92. Nampoothiri LP, Neelima PS, Rao AJ. Proteomic profiling of forskolin-induced differentiated BeWo cells: an in-vitro model of cytotrophoblast differentiation. Reprod Biomed Online. 2007;14(4):477–487
  93. Kikuchi J, Furukawa Y, Hayashi N. Identification of novel p53-binding proteins by biomolecular interaction analysis combined with tandem mass spectrometry. Mol Biotechnol. 2003;23(3):203–212
  94. Korgun ET, Celik-Ozenci C, Acar N, Cayli S, Desoye G, Demir R. Location of cell cycle regulators cyclin B1, cyclin A, PCNA, Ki67 and cell cycle inhibitors p21, p27 and p57 in human first trimester placenta and deciduas. Histochem Cell Biol. 2006;125(6):615–624
  95. Olvera M, Harris S, Amezcua CA, McCourty A, Rezk S, Koo C, et al. Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease. Mod Pathol. 2001;14(10):1036–1042
  96. Bamberger A, Sudahl S, Bamberger CM, Schulte HM, Loning T. Expression patterns of the cell-cycle inhibitor p27 and the cell-cycle promoter cyclin E in the human placenta throughout gestation: implications for the control of proliferation. Placenta. 1999;20(5–6):401–406
  97. Bae SN, Kim J, Lee YS, Kim JD, Kim MY, Park LO. Cytotoxic effect of zinc-citrate compound on choriocarcinoma cell lines. Placenta. 2007;28(1):22–30[Epub 2006 Feb 28]
  98. Yamada Z, Kitagawa M, Takemura T, Hirokawa K. Effect of maternal age on indices of apoptotic and proliferative cells in trophoblasts of full-term placenta. Mol Hum Reprod. 2001;7(12):1179–1185
  99. Danihel L, Gomolcak P, Korbel M, Pruzinec J, Vojtassak J, Janik P, et al. Expression of proliferation and apoptotic markers in human placenta during pregnancy. Acta Histochem. 2002;104(4):335–338
  100. Axt-Fliedner R, Friedrich M, Kordina A, Wasemann C, Mink D, Reitnauer K, et al. The immunolocalization of Bcl-2 in human term placenta. Clin Exp Obstet Gynecol. 2001;28(3):144–147
  101. Huppertz B, Frank HG, Kingdom JC, Reister F, Kaufmann P. Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem Cell Biol. 1998;110(5):495–508
  102. Hu C, Smith SD, Pang L, Sadovsky Y, Nelson DM. Enhanced basal apoptosis in cultured term human cytotrophoblasts is associated with a higher expression and physical interaction of p53 and Bak. Placenta. 2006;27(9–10):978–983[Epub 2005 Dec 27]
  103. Charles AK, Hisheh S, Liu D, Rao RM, Waddell BJ, Dickinson JE, et al. The expression of apoptosis related genes in the first trimester human placenta using a short term in vitro model. Apoptosis. 2005;10(1):135–140
  104. Qiao S, Nagasaka T, Harada T, Nakashima N. p53, Bax and Bcl-2 expression, and apoptosis in gestational trophoblast of complete hydatidiform mole. Placenta. 1998;19(5–6):361–369
  105. Soleymanlou N, Wu Y, Wang JX, Todros T, Ietta F, Jurisicova A, et al. A novel Mtd splice isoform is responsible for trophoblast cell death in pre-eclampsia. Cell Death Differ. 2005;12(5):441–452
  106. Stepan H, Leo C, Purz S, Hockel M, Horn LC. Placental localization and expression of the cell death factors BNip3 and Nix in preeclampsia, intrauterine growth retardation and HELLP syndrome. Eur J Obstet Gynecol Reprod Biol. 2005;122(2):172–176
  107. Ka H, Hunt JS. Temporal and spatial patterns of expression of inhibitors of apoptosis in human placentas. Am J Pathol. 2003;163(2):413–422
  108. Shiozaki A, Kataoka K, Fujimura M, Yuki H, Sakai M, Saito S. Survivin inhibits apoptosis in cytotrophoblasts. Placenta. 2003;24(1):65–76
  109. Gruslin A, Qiu Q, Tsang BK. X-linked inhibitor of apoptosis protein expression and the regulation of apoptosis during human placental development. Biol Reprod. 2001;64(4):1264–1272
  110. Straszewski-Chavez SL, Visintin IP, Karassina N, Los G, Liston P, Halaban R, et al. XAF1 mediates tumor necrosis factor-alpha-induced apoptosis and X-linked inhibitor of apoptosis cleavage by acting through the mitochondrial pathway. J Biol Chem. 2007;282(17):13059–13072[Epub 2007 Feb 28]
  111. Heazell AE, Buttle H, Baker PN, Crocker IP. Altered expression of regulators of caspase activity within trophoblast of normal and pre-eclamptic pregnancies. Reprod Sci. 2007;14(1):266A
  112. Hung TH, Skepper JN, Charnock-Jones DS, Burton GJ. Hypoxia-reoxygenation: a potent inducer of apoptotic changes in the human placenta and possible etiological factor in preeclampsia. Circ Res. 2002;90(12):1274–1281
  113. Huppertz B, Kingdom J, Caniggia I, Desoye G, Black S, Korr H, et al. Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta. 2003;24(2–3):181–190
  114. Crocker IP, Tansinda DM, Jones CJ, Baker PN. The influence of oxygen and tumor necrosis factor-alpha on the cellular kinetics of term placental villous explants in culture. J Histochem Cytochem. 2004;52(6):749–757
  115. Kam DW, Charles AK, Dharmarajan AM. Caspase-14 expression in the human placenta. Reprod Biomed Online. 2005;11(2):236–243
  116. Jeschke U, Schiessl B, Mylonas I, Kunze S, Kuhn C, Schulze S, et al. Expression of the proliferation marker Ki-67 and of p53 tumor protein in trophoblastic tissue of preeclamptic, HELLP, and intrauterine growth-restricted pregnancies. Int J Gynecol Pathol. 2006;25(4):354–360
  117. Sgarbosa F, Barbisan LF, Brasil MA, Costa E, Calderon IM, Goncalves CR, et al. Changes in apoptosis and Bcl-2 expression in human hyperglycemic, term placental trophoblast. Diabetes Res Clin Pract. 2006;73(2):143–149[Epub 2006 Mar 24]
  118. Soleymanlou N, Jurisicova A, Wu Y, Chijiiwa M, Ray JE, Detmar J, et al. Hypoxic switch in mitochondrial myeloid cell leukemia factor-1/Mtd apoptotic rheostat contributes to human trophoblast cell death in preeclampsia. Am J Pathol. 2007;171(2):496–506
  119. Levy R, Smith SD, Chandler K, Sadovsky Y, Nelson DM. Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor. Am J Physiol Cell Physiol. 2000;278(5):C982–C988
  120. Heazell AE, Lacey HA, Jones CJ, Huppertz B, Baker PN, Crocker IP. Effects of oxygen on cell turnover and expression of regulators of apoptosis in human placental trophoblast. Placenta. 2008 Feb;29(2):175–186[Epub 2007 Dec 21]
  121. Hu R, Zhou S, Li X. Altered Bcl-2 and Bax expression is associated with cultured first trimester human cytotrophoblasts apoptosis induced by hypoxia. Life Sci. 2006;79(4):351–355[Epub 2006 Feb 24]
  122. Goswami D, Tannetta DS, Magee LA, Fuchisawa A, Redman CW, Sargent IL, et al. Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction. Placenta. 2006;27(1):56–61[Epub 2005 Jan 25]
  123. Knight M, Redman CW, Linton EA, Sargent IL. Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br J Obstet Gynaecol. 1998;105(6):632–640
  124. Zhong XY, Holzgreve W, Hahn S. The levels of circulatory cell free fetal DNA in maternal plasma are elevated prior to the onset of preeclampsia. Hypertens Pregnancy. 2002;21(1):77–83
  125. Abumaree MH, Stone PR, Chamley LW. An in vitro model of human placental trophoblast deportation/shedding. Mol Hum Reprod. 2006;12(11):687–694[Epub 2006 Sep 20]
  126. Orozco AF, Bischoff FZ, Horne C, Popek E, Simpson JL, Lewis DE. Hypoxia-induced membrane-bound apoptotic DNA particles: potential mechanism of fetal DNA in maternal plasma. Ann N Y Acad Sci. 2006;1075:57–62
  127. Tjoa ML, Cindrova-Davies T, Spasic-Boskovic O, Bianchi DW, Burton GJ. Trophoblastic oxidative stress and the release of cell-free feto-placental DNA. Am J Pathol. 2006;169(2):400–404
  128. Abumaree MH, Stone PR, Chamley LW. The effects of apoptotic, deported human placental trophoblast on macrophages: possible consequences for pregnancy. J Reprod Immunol. 2006;72(1–2):33–45[Epub 2006 Jul 14]
  129. Sargent IL, Germain SJ, Sacks GP, Kumar S, Redman CW. Trophoblast deportation and the maternal inflammatory response in pre-eclampsia. J Reprod Immunol. 2003;59(2):153–160
  130. Gupta A, Hasler P, Gebhardt S, Holzgreve W, Hahn S. Occurrence of neutrophil extracellular DNA traps (NETs) in pre-eclampsia: a link with elevated levels of cell-free DNA?. Ann N Y Acad Sci. 2006;1075:118–122
  131. Gupta AK, Rusterholz C, Huppertz B, Malek A, Schneider H, Holzgreve W, et al. A comparative study of the effect of three different syncytiotrophoblast micro-particles preparations on endothelial cells. Placenta. 2005;26(1):59–66
  132. Hoegh AM, Tannetta D, Sargent I, Borup R, Nielsen FC, Redman C, et al. Effect of syncytiotrophoblast microvillous membrane treatment on gene expression in human umbilical vein endothelial cells. BJOG. 2006;113(11):1270–1279
  133. Cockell AP, Learmont JG, Smarason AK, Redman CW, Sargent IL, Poston L. Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function. Br J Obstet Gynaecol. 1997;104(2):235–240
  134. Nevo O, Soleymanlou N, Wu Y, Xu J, Kingdom J, Many A, et al. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol. 2006;291(4):R1085–R1093
  135. Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005
  136. Guller S, Ma Y, Di Santo S, Krikun G, Malek A, Schneider H. Microparticles shed from human placenta contain anti-fibrinolytic and anti-angiogenic compounds: implications in pre-eclampsia. Reprod Sci. 2007;14(Suppl 1):219A
  137. Newhouse SM, Davidge ST, Winkler-Lowen B, Demianczuk N, Guilbert LJ. In vitro differentiation of villous trophoblasts from pregnancies complicated by intrauterine growth restriction with and without pre-eclampsia. Placenta. 2007;28(10):999–1003

PII: S0143-4004(08)00208-7

doi: 10.1016/j.placenta.2008.07.003

Placenta
Volume 29, Issue 9 , Pages 772-783 , September 2008