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  • Print publication year: 2007
  • Online publication date: September 2009

1 - Trophoblast invasion in pre-eclampsia and other pregnancy disorders

from Part I - Basic science

Summary

Trophoblast invasion is a major feature of hemochorial placentation, notably in the human where this invasion is exceptionally deep compared with the few other primate species studied so far (Ramsey et al., 1976). It is assumed that pre-eclampsia/eclampsia, which occurs almost exclusively in the human species, is in some way associated with problems related to this deep invasion. So far, only a few case reports have been published suggesting a similar complication in pregnant gorillas (Baird, 1981; Thornton and Onwude, 1992). Unfortunately nothing is known about trophoblast invasion in this species.

It is now common knowledge that during pregnancy extensive vascular alterations take place in the spiral arteries which supply maternal blood to the placenta. In this chapter we will first sketch briefly the historical context of the discovery of structural changes in placental bed spiral arteries and the role of invading extravillous trophoblast. The importance of this “physiological change” of spiral arteries is highlighted by its restricted occurrence in pre-eclampsia, and therefore we will discuss next the evidence for impaired trophoblast invasion preceding the onset of clinical symptoms of pre-eclampsia. In the third part the structural features of invaded and non-invaded spiral arteries will be described in some detail, and finally we will evaluate the occurrence of physiological changes and vascular lesions in other disorders of pregnancy.

Impaired physiological change in spiral arteries

Although pre-eclampsia/eclampsia has been recognized for a long time in history as an important pregnancy complication (Lindheimer et al. 1999), a possible histopathological basis for this condition was only identified in the late 1960s.

REFERENCES
Aardema, M. W., Oosterhof, H., Timmer, A., Rooy, I. and Aarnoudse, J. G. (2001). Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by pre-eclampsia and small for gestational age fetuses. Placenta, 22, 405–11.
Ashton, S. V., Whitley, G. StJ., Dash, P. R., Wareing, M., Crocker, I. P., Baker, P. N. and Cartwright, J. E. (2005). Uterine spiral artery remodeling involves endothelial apoptosis induced by extravillous trophoblasts through Fas/FasL interactions. Arterioscler. Thromb. Vasc. Biol., 25, 102–8.
Baird, J. N. Jr. (1981). Eclampsia in a lowland gorilla. Am. J. Obstet. Gynecol., 141, 345–6.
Björk, O., Persson, B., Stangenberg, M. and Vaclavinkova, V. (1984). Spiral artery lesions in relation to metabolic control in diabetes mellitus. Acta Obstet. Gynecol. Scand., 63, 123–7.
Boyd, J. D. and Hamilton, W. J. (1970). The Human Placenta. Cambridge: W. Heffer.
Brosens, I. A. (1977). Morphological changes in the utero-placental bed in pregnancy hypertension. Clin. Obstet. Gynaecol., 4, 573–93.
Brosens, I. A. (1988). The utero-placental vessels at term – the distribution and extent of the physiological changes. Trophoblast Res., 3, 61–7.
Brosens, I. and Renaer, M. (1972). On the pathogenesis of placental infarcts in pre-eclampsia. J. Obstet. Gynaec. Br. Cwlth, 79, 794–9.
Brosens, I., Robertson, W. B. and Dixon, H. G. (1967). The physiological response of the vessels of the placental bed to normal pregnancy. J. Path. Bact., 93, 569–79.
Brosens, I. A., Robertson, W. B. and Dixon, H. G. (1972). The role of spiral arteries in the pathogenesis of preeclampsia. In Obstetrics and Gynecology Annual, ed. Wynn, R. M.. New York: Appleton-Century-Crofts, pp. 177–91.
Brosens, I., Dixon, H. G. and Robertson, W. B. (1977). Fetal growth retardation and the arteries of the placental bed. Br. J. Obstet. Gynaecol., 84, 656–63.
Brosens, J. J., Pijnenborg, R. and Brosens, I. (2002). The myometrial junctional zone spiral arteries in normal and abnormal pregnancies. Am. J. Obstet. Gynecol., 187, 1416–23.
Brown, M. A., Hague, W. M., Higgins, J., et al. (2000). The detection, investigation and management of hypertension in pregnancy: full consensus statement. Aust. N. Z. J. Obstet. Gynaecol., 40, 139–55.
Browne, J. C. M. and Veall, N. (1953). The maternal placental blood flow in normotensive and hypertensive women. J. Obstet. Gyn. Br. Emp., 60, 141–8.
Bulmer, J. N., Billington, W. D. and Johnson, P. M. (1984). Immunohistologic identification of trophoblast populations in early human pregnancy with the use of monoclonal antibodies. Am. J. Obstet. Gynecol., 148, 19–26.
Damsky, C. H., Fitzgerald, M. L. and Fisher, S. J. (1992). Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo. J. Clin. Invest., 89, 210–22.
Davey, D. A. and MacGillivray, I. (1988). The classification and definition of the hypertensive disorders of pregnancy. Am. J. Obstet. Gynecol., 158, 892–989.
Wolf, F., Carreras, L. O., Moerman, P., Vermylen, J., Assche, A. and Renaer, M. (1982). Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant. Am. J. Obstet. Gynecol., 142, 829–34.
DiFederico, E., Genbacev, O. and Fisher, S. J. (1999). Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. Am. J. Pathol., 155, 293–301.
Dixon, H. G. and Robertson, W. B. (1958). A study of the vessels of the placental bed in normotensive and hypertensive women. J. Obstet. Gyn. Br. Emp., 65, 803–9.
Emmrich, P., Birke, R. and Gödel, E. (1975). Beitrag zur Morphologie der myometrialen und dezidualen Arterien bei normalen Schwangerschaften, EPH-Gestosen und mütterlichem Diabetes mellitus. Path. Microbiol., 43, 38–61.
Frusca, T., Morassi, L., Pecorelli, S., Grigolato, P. and Gastaldi, A. (1989). Histological features of uteroplacental vessels in normal and hypertensive patients in relation to birthweight. Br. J. Obstet. Gynaecol., 96, 835–9.
Gerretsen, G., Huisjes, H. J. and Elema, J. D. (1981). Morphological changes of the spiral arteries in the placental bed in relation to pre-eclampsia and fetal growth retardation. Br. J. Obstet. Gynaecol., 88, 876–81.
Gerretsen, G., Huisjes, H. J., Hardonk, M. J. and Elema, J. D. (1983). Trophoblast alterations in the placental bed in relation to physiological changes in spiral arteries. Br. J. Obstet. Gynaecol., 90, 34–9.
Hamilton, W. J. and Boyd, J. D. (1960). Development of the human placenta in the first three months of gestation. J. Anat., 94, 297–328.
Hanssens, M., Pijnenborg, R., Keirse, M. J. N. C., Vercruysse, L., Verbist, L. and Assche, F. A. (1998). Renin-like immunoreactivity in uterus and placenta from normotensive and hypertensive pregnancies. Eur. J. Obstet. Gynecol. Reprod. Biol., 81, 177–84.
Harris, J. W. S. and Ramsey, E. M. (1966). The morphology of human uteroplacental vasculature. Contrib. Embryol., 38, 43–58.
Hertig, A. T. (1945). Vascular pathology in the hypertensive albuminuric toxaemias of pregnancy. Clinics, 4, 602–14.
Huppertz, B., Kertschanska, S., Demir, A. Y., Frank, H.-G. and Kaufmann, P. (1998). Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta. Cell Tissue Res., 291, 133–48.
Hustin, J., Foidart, J. M. and Lambotte, R. (1983). Maternal vascular lesions in pre-eclampsia and intrauterine growth retardation: light microscopy and immunofluorescence. Placenta, 4, 489–98.
Hustin, J., Jauniaux, E. and Schaaps, J. P. (1990). Histological study of the materno-embryonic interface in spontaneous abortion. Placenta, 11, 477–86.
Jauniaux, E. and Burton, G. J. (2006). Villous histomorphometry and placental bed biopsy investigation in type I diabetic pregnancies. Placenta, 27, 468–74.
Kam, E. P. Y., Gardner, L., Loke, Y. W. and King, A. (1999). The role of trophoblast in the physiological change in decidual spiral arteries. Hum. Reprod., 14, 2131–8.
Keith, J. C. Jr., Pijnenborg, R., Spitz, B., Hanssens, M. and Assche, F. A. (1995). Assessment of differential serum cytotoxicity in gestational hypertension using a fibrosarcoma cell line and the MTT assay. Hypertens. Pregnancy, 14, 81–90.
Khong, T. Y. (1991). Acute atherosis in pregnancies complicated by hypertension, small-for-gestational-age infants, and diabetes mellitus. Arch. Pathol. Lab. Med., 115, 722–5.
Khong, T. Y. and Robertson, W. B. (1992). Spiral artery disease. In Immunological Obstetrics, ed. Coulam, C. B., Faulk, W. P. and McIntyre, J.. New York, Norton, pp. 492–501.
Khong, T. Y., Wolf, F., Robertson, W. B. and 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, 1049–59.
Khong, T. Y., Liddell, H. S. and Robertson, W. B. (1987). Defective haemochorial placentation as a cause of miscarriage: a preliminary study. Br. J. Obstet. Gynaecol., 94, 649–55.
Kim, Y. M., Chaiworapongsa, T., Gomez, R., et al. (2002). Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes. Am. J. Obstet. Gynecol., 187, 1137–42.
Kitzmiller, J. L. and Benirschke, K. (1973). Immunofluorescent study of placental bed vessels in pre-eclampsia of pregnancy. Am. J. Obstet. Gynecol., 115, 248–51.
Labarrere, C. A. (1988). Acute atherosis. A histopathological hallmark of immune aggression?Placenta, 9, 95–108.
Lendrum, A. C. (1963). The hypertensive diabetic kidney as a model of the so-called collagen diseases. Canad. Med. Ass. J., 88, 442–52.
Lin, S., Shimizu, I., Suehara, N., Nakayama, M. and Aono, T. (1995). Uterine artery Doppler velocimetry in relation to trophoblast migration into the myometrium of the placental bed. Obstet. Gynecol., 85, 760–5.
Lindheimer M. D., Roberts, J. M., Cunningham, F. G. and Chesley, L. (1999). Introduction, history, controversies, and definitions. In Chesley's Hypertensive Disorders in Pregnancy, eds. Lindheimer, M. D., Roberts, J. M. and Cunningham, F. G.. Stamford, CT: Appleton & Lange, pp. 3–41.
Lyall, F. (2002). The human placental bed revisited. Placenta, 23, 555–62.
Lyall, F., Bulmer, J. N., Duffie, E., Cousins, F., Theriault, A. and Robson, S. C. (2001a). Human trophoblast invasion and spiral artery transformation. The role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction. Am. J. Pathol., 158, 1713–21.
Lyall, F., Simpson, H., Bulmer, J. N., Barber, A. and Robson, S. C. (2001b). Transforming growth factor-β expression in human placenta and placental bed in third trimester normal pregnancy, preeclampsia, and fetal growth restriction. Am. J. Pathol., 159, 1827–38.
MacGillivray, I. (1983). Pre-eclampsia, the Hypertensive Disease of Pregnancy. London: WB Saunders Company Ltd, pp. 78–82.
Magid, M. S., Kaplan, C., Sammaritano, L. R., Peterson, M., Druzin, M. L. and Lockshin, M. D. (1998). Placental pathology in systemic lupus erythematosus: a prospective study. Am. J. Obstet. Gynecol., 179, 226–34.
Matijevic, R. and Johnston, T. (1999). In vivo assessment of failed trophoblastic invasion of the spiral arteries in pre-eclampsia. Br. J. Obstet. Gynaecol., 106, 78–82.
Matijevic, R., Meekins, J. W., Walkinshaw, S. A., Neilson, J. P. and McFadyen, I. R. (1995). Spiral artery blood flow in the central and peripheral areas of the placental bed in the second trimester. Obstet. Gynecol., 86, 289–92.
McFadyen, I. R., Price, A. B. and Geirsson, R. T. (1986). The relation of birthweight to histological appearances in vessels of the placental bed. Br. J. Obstet. Gynaecol., 93, 476–81.
McParland, P. and Pearce, J. M. (1988). Doppler blood flow in pregnancy. Placenta, 9, 427–50.
Meekins, J. W., Pijnenborg, R., Hanssens, M., McFadyen, I. R. and Assche, A. (1994a). A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol., 101, 669–74.
Meekins, J. W., Pijnenborg, R., Hanssens, M., Assche, A. and McFadyen, I. R. (1994b). Immunohistochemical detection of lipoprotein(a) in the wall of placental bed spiral arteries in normal and severe pre-eclamptic pregnancies. Placenta, 15, 511–24.
Moodley, J. and Ramsaroop, R. (1989). Placental bed morphology in black women with eclampsia. S. Afr. Med. J., 75, 376–8.
Naicker, T., Khedun, S. M., Moodley, J. and Pijnenborg, R. (2003). Quantitative analysis of trophoblast invasion in pre-eclampsia. Acta Obstet. Gynecol. Scand., 82, 722–9.
Olofsson, P. (1993). A high uterine artery pulsatility index reflects a defective development of placental bed spiral arteries in pregnancies complicated by hypertension and fetal growth retardation. Eur. J. Obstet. Gynecol. Reprod. Biol., 49, 161–8.
Pijnenborg, R. (1996). The placental bed. Hypertens. Pregnancy, 15, 7–23.
Pijnenborg, R., Anthony, J., Davey, D. A., et al. (1991). Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br. J. Obstet. Gynaecol., 98, 648–55.
Pijnenborg, R., Bland, J. M., Robertson, W. B. and Brosens, I. (1983). Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy. Placenta, 4, 397–414.
Pijnenborg, R., Bland, J. M., Robertson, W. B., Dixon, G. and Brosens, I. (1981). The pattern of interstitial trophoblastic invasion of the myometrium in early human pregnancy. Placenta, 2, 303–16.
Pijnenborg, R., Dixon, G., Robertson, W. B. and Brosens, I. (1980). Trophoblastic invasion of human decidua from 8 to 18 weeks of pregnancy. Placenta, 1, 3–19.
Pijnenborg, R., McLaughlin, P. J., Vercruysse, L., et al. (1998b). Immunolocalization of tumor necrosis factor-α (TNF-α) in the placental bed of normotensive and hypertensive human pregnancies. Placenta, 19, 231–9.
Pijnenborg, R., Vercruysse, L., Ballegeer, V., et al. (1992). The distribution of fibronectin in the placental bed in normotensive and hypertensive human pregnancies. Trophoblast Res., 6, 343–50.
Pijnenborg, R., Vercruysse, L. and Hanssens, M. (2006). The uterine spiral arteries in human pregnancy: facts and controversies. Placenta, 27, 939–58.
Pijnenborg, R., Vercruysse, L., Verbist, L. and Assche, F. A. (1998a). Interaction of interstitial trophoblast with placental bed capillaries and venules of normotensive and pre-eclamptic pregnancies. Placenta, 19, 569–75.
Pinkerton, J. H. M. (1963). The placental bed arterioles in diabetes. Proc. R. Soc. Med., 56, 1021–2.
Ramsey, E. M., Houston, M. L. and Harris, J. W. S. (1976). Interactions of the trophoblast and maternal tissues in three closely related primate species. Am. J. Obstet. Gynecol., 124, 647–52.
Reister, F., Frank, H.-G., Kingdom, J. C. P., et al. (2001). Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women. Lab. Invest., 81, 1143–52.
Roberts, J. M. and Lain, K. Y. (2002). Recent insights into the pathogenesis of pre-eclampsia. Placenta, 23, 359–72.
Robertson, W. B., Brosens, I. and Dixon, H. G. (1967). The pathological response of the vessels of the placental bed to hypertensive pregnancy. J. Path. Bact., 93, 581–92.
Robertson, W. B., Khong, T. Y., Brosens, I., Wolf, F., Sheppard, B. L. and Bonnar, J. (1986). The placental bed biopsy: review from three European centres. Am. J. Obstet. Gynecol., 155, 401–12.
Robson, S. C., Ball, E., Lyall, F., Simpson, H., Ayis, S. and Bulmer, J. (2001). Endovascular trophoblast invasion and spiral artery transformation: the ‘two wave' theory revisited. Placenta, 22, A.25.
Robson, S. C., Simpson, H., Ball, E., Lyall, F. and Bulmer, J. N. (2002). Punch biopsy of the human placental bed. Am. J. Obstet. Gynecol., 187, 1349–55.
Sagol, S., Özkinay, E., Öztekin, K. and Özdemir, N. (1999). The comparison of uterine artery Doppler velocimetry with the histopathology of the placental bed. Aust. N. Z. J. Obstet. Gynaec., 39, 324–9.
Sebire, N. J., Fox, H., Backos, M., Rai, R., Paterson, C. and Regan, L. (2002). Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure. Hum. Reprod., 17, 1067–71.
Sheppard, B. L. and Bonnar, J. (1976). The ultrastructure of the arterial supply of the human placenta in pregnancy complicated by fetal growth retardation. Br. J. Obstet. Gynaecol., 83, 948–59.
Sheppard, B. L. and Bonnar, J. (1981). An ultrastructural study of utero-placental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation. Br. J. Obstet. Gynaecol., 88, 695–705.
Starzyk, K. A., Salafia, C. M., Pezzullo, J. C., et al. (1997). Quantitative differences in arterial morphometry define the placental bed in preeclampsia. Hum. Pathol., 28, 353–8.
Stone, S., Pijnenborg, R., Vercruysse, L., et al. (2006). The placental bed in pregnancies complicated by primary antiphospholipid syndrome. Placenta, 27, 457–67.
Thornton, J. G. and Onwude, J. L. (1992). Convulsions in pregnancy in related gorillas. Am. J. Obstet. Gynecol., 167, 240–1.
Voigt, H. J. and Becker, V. (1992). Doppler flow measurements and histomorphology of the placental bed in uteroplacental insufficiency. J. Perinat. Med., 20, 139–47.
Yui, J., Garcia-Lloret, M., Wegmann, T. G. and Guilbert, L. J. (1994). Cytotoxicity of tumor necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts. Placenta, 15, 819–35.
Zeek, P. M. and Assali, N. S. (1950). Vascular changes in the decidua associated with eclamptogenic toxemia of pregnancy. Am. J. Clin. Path., 20, 1099–109.
Zhou, Y., Damsky, C. H., Chiu, K., Roberts, J. M. and Fisher, S. J. (1993). Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts. J. Clin. Invest., 91, 950–60.
Zhou, Y., Damsky, C. H. and Fisher, S. J. (1997b). Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. J. Clin. Invest., 99, 2152–64.
Zhou, Y., Fisher, S. J., Janatpour, M. J., et al. (1997a). Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?J. Clin. Invest., 99, 2139–51.