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  • Print publication year: 2010
  • Online publication date: October 2010

Chapter 21 - Trophoblast biology and early pregnancy


Venous thromboembolism (VTE) has a multifactorial pathogenesis involving genetic predisposition, acquired diseases and conditions, and lifestyle and environmental factors. Although the level of risk of VTE associated with air travel has been exaggerated through sensationalized reporting in the mass media, it has nevertheless been established now that long-haul flights represent a risk factor for deep vein thrombosis and pulmonary embolism, including fatal events. Potentially effective measures to reduce the risk of travel-related VTE include enhanced mobility, use of graduated compression hosiery and pharmacological interventions. Low molecular weight heparin (LMWH) is effective in reducing the incidence of VTE post-operatively (by 50-60%) as well as in hospitalized subjects more generally, with little increased risk of bleeding. Based on the low absolute risk of travel-related VTE in the overwhelming majority of women during early pregnancy, pharmacological thromboprophylaxis with LMWH can be justified.

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1. BoydJD, HamiltonWJ. The Human Placenta. Cambridge, MA: W Heffer and Sons, 1970.
2. WulffC, WeigandM, KreienbergR, FraserHM. Angiogenesis during primate placentation in health and disease. Reproduction 2003; 126: 569–77.
3. MakikallioK, TekayA, JouppilaP. Yolk sac and umbilicoplacental hemodynamics during early human embryonic development. Ultrasound Obstet Gynecol 1999; 14: 175–9.
4. FrankHG, KaufmannP. Nonvillous parts and trophoblast invasion. In K Benirschke, P Kaufmann, R Baergen (eds.), Pathology of the Human Placenta. 5th edition.. New York: Springer, 2006, pp. 191–312.
5. BrosensI, RobertsonWB, DixonHG. The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bacteriol 1967; 93: 569–79.
6. HarrisLK, KeoghRJ, WareingMet al. Invasive trophoblasts stimulate vascular smooth muscle cell apoptosis by a fas ligand-dependent mechanism. Am J Pathol 2006; 169: 1863–74.
7. HarrisLK, KeoghRJ, WareingMet al. BeWo cells stimulate smooth muscle cell apoptosis and elastin breakdown in a model of spiral artery transformation. Hum Reprod 2007; 22: 2834–41.
8. KeoghRJ, HarrisLK, FreemanAet al. Fetal-derived trophoblast use the apoptotic cytokine tumor necrosis factor-alpha-related apoptosis-inducing ligand to induce smooth muscle cell death. Circ Res 2007; 100: 834–41.
9. ChenQ, StonePR, McCowanLM, ChamleyLW. Interaction of Jar choriocarcinoma cells with endothelial cell monolayers. Placenta 2005; 26: 617–25.
10. GomezO, FiguerasF, MartinezJMet al. Sequential changes in uterine artery blood flow pattern between the first and second trimesters of gestation in relation to pregnancy outcome. Ultrasound Obstet Gynecol 2006; 28: 802–8.
11. PlasenciaW, MaizN, PoonL, YuC, NicolaidesKH. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol 2008; 32: 138–46.
12. GroomKM, NorthRA, StonePRet al. Patterns of change in uterine artery Doppler studies between 20 and 24 weeks of gestation and pregnancy outcomes. Obstet Gynecol 2009; 113: 332–8.
13. FoidartJM, HustinJ, DuboisM, SchaapsJP. The human placenta becomes haemochorial at the 13th week of pregnancy. Int J Dev Biol 1992; 36: 451–3.
14. JauniauxE, WatsonA, BurtonG. Evaluation of respiratory gases and acid-base gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks’ gestation. Am J Obstet Gynecol 2001; 184: 998–1003.
15. JauniauxE, WatsonAL, HempstockJet al. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol 2000; 157: 2111–22.
16. KhongTY, De WolfF, RobertsonWB, BrosensI. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol 1986; 93: 1049–59.
17. RobertsonWB, BrosensI, DixonHG. The pathological response of the vessels of the placental bed to hypertensive pregnancy. J Pathol Bacteriol 1967; 93: 581–92.
18. NaickerT, KhedunSM, MoodleyJ, PijnenborgR. Quantitative analysis of trophoblast invasion in preeclampsia. Acta Obstet Gynecol Scand 2003; 82: 722–9.
19. BallE, BulmerJN, AyisS, LyallF, RobsonSC. Late sporadic miscarriage is associated with abnormalities in spiral artery transformation and trophoblast invasion. J Pathol 2006; 208: 535–42.
20. BallE, RobsonSC, AyisS, LyallF, BulmerJN. Early embryonic demise: no evidence of abnormal spiral artery transformation or trophoblast invasion. J Pathol 2006; 208: 528–34.
21. SebireNJ, FoxH, BackosMet al. Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure. Hum Reprod 2002; 17: 1067–71.
22. ChienPF, ArnottN, GordonA, OwenP, KhanKS. How useful is uterine artery Doppler flow velocimetry in the prediction of pre-eclampsia, intrauterine growth retardation and perinatal death? An overview. BJOG 2000; 107: 196–208.
23. HuppertzB. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension 2008; 51: 970–5.
24. MeekinsJW, PijnenborgR, HanssensM, McFadyenIR, van AssheA. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol 1994; 101: 669–74.
25. JauniauxE, HempstockJ, GreenwoldN, BurtonGJ. 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: 115–25.
26. JauniauxE, GreenwoldN, HempstockJ, BurtonGJ. Comparison of ultrasonographic and Doppler mapping of the intervillous circulation in normal and abnormal early pregnancies. Fertil Steril 2003; 79: 100–6.
27. LashGE, AnsariT, BischofPet al. IFPA meeting 2008 workshops report. Placenta 2009; 30: S4–S14.
28. CaniggiaI, Grisaru-GravnoskyS, KuliszewskyM, PostM, LyeSJ. Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest 1999; 103: 1641–50.
29. CaniggiaI, LyeSJ, CrossJC. Activin is a local regulator of human cytotrophoblast cell differentiation. Endocrinology 1997; 138: 3976–86.
30. HamiltonGS, LysiakJJ, WatsonAJ, LalaPK. Effects of colony stimulating factor-1 on human extravillous trophoblast growth and invasion. J Endocrinol 1998; 159: 69–77.
31. HamiltonGS, LysiakJJ, HanVK, LalaPK. Autocrine-paracrine regulation of human trophoblast invasiveness by insulin-like growth factor (IGF)-II and IGF-binding protein (IGFBP)-1. Exp Cell Res 1998; 244: 147–56.
32. ConstanciaM, HembergerM, HughesJet al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 2002; 417: 945–8.
33. SchmorlG. Pathologisch-Anatomische Untersuchungen Uber Puerperal-Eklampsie. Verlag von FC Vogel: Leipzig, 1893.
34. AttwoodHD, ParkWW. Embolism to the lungs by trophoblast. J Obstet Gynaecol Br Commonw 1961; 68: 611–17.
35. AbumareeMH, StonePR, ChamleyLW. An in vitro model of human placental trophoblast deportation/shedding. Mol Hum Reprod 2006; 12: 687–94.
36. CovoneAE, MuttonD, JohnsonPM, AdinolfiM. Trophoblast cells in peripheral blood from pregnant women. Lancet 1984; 2: 841–3.
37. HawesCS, SuskinHA, PetropoulosA, LathamSE, MuellerUW. A morphologic study of trophoblast isolated from peripheral blood of pregnant women. Am J Obstet Gynecol 1994; 170: 1297–300.
38. JohansenM, RedmanCW, WilkinsT, SargentIL. Trophoblast deportation in human pregnancy – its relevance for pre-eclampsia. Placenta 1999; 20: 531–9.
39. ChuaS, WilkinsT, SargentI, RedmanC. Trophoblast deportation in pre-eclamptic pregnancy. Br J Obstet Gynaecol 1991; 98: 973–9.
40. KnightM, RedmanCW, LintonEA, SargentIL. Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br J Obstet Gynaecol 1998; 105: 632–40.
41. BittencourtMC, PerrucheS, ContassotEet al. Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers. Blood 2001; 98: 224–30.
42. AbumareeMH, StonePR, ChamleyLW. The effects of apoptotic, deported human placental trophoblast on macrophages: possible consequences for pregnancy. J Reprod Immunol 2006; 72: 33–45.
43. ChenQ, StonePR, McCowanLM, ChamleyLW. Phagocytosis of necrotic but not apoptotic trophoblasts induces endothelial cell activation. Hypertension 2006; 47: 116–21.
44. SullivanAE, SilverRM, LaCoursiereDY, PorterTF, BranchDW.Recurrent fetal aneuploidy and recurrent miscarriage. Obstet Gynecol 2004; 104: 784–8.
45. JohnsJ, MuttukrishnaS, LygnosM, GroomeN, JauniauxE. Maternal serum hormone concentrations for prediction of adverse outcome in threatened miscarriage. Reprod Biomed Online 2007; 15: 413–21.
46. BarrettSL, BowerC, HadlowNC. Use of the combined first-trimester screen result and low PAPP-A to predict risk of adverse fetal outcomes. Prenat Diagn 2008; 28: 28–35.
47. RobinsonWP, BarrettIJ, BernardLet al. Meiotic origin of trisomy in confined placental mosaicism is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction. Am J Hum Genet 1997; 60: 917–27.
48. FarquharsonRG, QuenbyS, GreavesM. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 2002; 100: 408–13.
49. PattisonNS, ChamleyLW, BirdsallMet al. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am J Obstet Gynecol 2000; 183: 1008–12.
50. LaskinCA, SpitzerKA, ClarkCAet al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA trial. J Rheumatol 2009; 36: 279–87.
51. RaiR, CohenH, DaveM, ReganL. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). Br Med J 1997; 314: 253–7.
52. ChamleyLW. Antiphospholipid antibodies: biological basis and prospects for treatment. J Reprod Immunol 2002; 57: 185–202.
53. Di SimoneN, LuigiMP, MarcoDet al. Pregnancies complicated with antiphospholipid syndrome: the pathogenic mechanism of antiphospholipid antibodies: a review of the literature. Ann N Y Acad Sci 2007; 1108: 505–14.
54. BoseP, BlackS, KadyrovMet al. Adverse effects of lupus anticoagulant positive blood sera on placental viability can be prevented by heparin in vitro. Am J Obstet Gynecol 2004; 191: 2125–31.
55. BoseP, BlackS, KadyrovMet al. Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure. Am J Obstet Gynecol 2005; 192: 23–30.
56. Di SimoneN, CaliandroD, CastellaniRet al. Low-molecular weight heparin restores in-vitro trophoblast invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with antiphospholipid syndrome. Hum Reprod 1999; 14: 489–95.
57. GanapathyR, WhitleyGS, CartwrightJE, DashPR, ThilaganathanB. Effect of heparin and fractionated heparin on trophoblast invasion. Hum Reprod 2007; 22: 2523–7.