MATERNAL  HYPERTENSIVE DISORDERS

- PRE-ECLAMPSIA

 

The basic clinical definition is a “pregnancy-specific condition of increased blood pressure accompanied by proteinuria, edema, or both.” (1,2).                Preeclampsia / eclampsia may not be a disease, but a syndrome with many causes. Significantly, one of the most frequent findings in preeclampsia is decreased or absent trophoblast invasion of the maternal spiral arteries (3-7).    

Decreased or absent trophoblast invasion may be a consequence of primary defects in the invasive trophoblasts or in the environment that the trophoblasts are attempting to invade. Studies have shown that in some cases of preeclampsia there are abnormalities in trophoblast function, including, but not limited to:

-                    integrin expression (8,9),

-                    thrombomodulin gene expression (10),

-                    glycogen metabolism (11),

-                    decreased galactose alpha 1-3 galactose expression (12),

-                    expression of plasminogen activator inhibitor-1 (13).

-                    In an unusual clinical presentation, preeclampsia has been associated with trisomy 13, the chromosome that carries the gene for type IV collagen (14). Placental bed biopsy in this multiparous woman carrying a trisomy 13 fetus showed lack of trophoblast invasion of maternal spiral arteries. These trophoblasts may have had difficulty invading through the maternal ECM because of increased type IV collagen production.

 The most common clinical finding in cases of preeclampsia is that the invasive trophoblasts have reached the vicinity of the spiral arteries, but have not penetrated them (15-17), as can be seen from a placental bed biopsy in a typical case of preeclampsia . Failure to convert the maternal spiral arteries into low-resistance channels can induce the placenta to secrete vasoactive substances that result in maternal hypertension (18,19). If the maternal blood pressure rises significantly, the spiral arteries can be damaged and may even become occluded, leading to placental infarction (20-22).

 

 

REFERENCES
  1. Cunningham FG, MacDonald PC, Gant NF et.al. Williams Obstetrics, 20th Edition. Stamford, Appleton & Lange, 1997

2.      Pijnenborg R, Vercruysse L, Verbist L, Van Assche FA: Interaction of interstitial trophoblast with placental bed capillaries and venules of normotensive and pre-eclamptic pregnancies. Placenta 1998, 19:569-75

  1. Robertson WB, Brosens I, Landells WN: Abnormal placentation. Obstet Gynecol Annu 1985, 14:411-26

4.      Pijnenborg R, Anthony J, Davey DA et.al. Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol 1991, 98:648-55

  1. Sheppard BL, Bonnar J: An ultrastructural study of utero-placental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation. Br J Obstet Gynaecol 1981, 88:695-705
  2. Sheppard BL, Bonnar J: The ultrastructure of the arterial supply of the human placenta in pregnancy complicated by fetal growth retardation. Br J Obstet Gynaecol 1976, 83:948-59
  3. Gerretsen G, Huisjes HJ, Hardonk MJ, Elema JD: Trophoblast alterations in the placental bed in relation to physiological changes in spiral arteries. Br J Obstet Gynaecol 1983, 90:34-9
  4. Zhou Y, Damsky CH, Fisher SJ: 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, 99:2152-64
  5. Lim KH, Zhou Y, Janatpour M et.al. Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia. Am J Pathol 1997, 151:1809-18
  6. Nakabayashi M, Yamamoto S, Suzuki K: Analysis of thrombomodulin gene polymorphism in women with severe early-onset preeclampsia. Semin Thromb Hemost 1999, 25:473-9
  7. Arkwright PD, Rademacher TW, Dwek RA, Redman CW: Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles. J Clin Invest 1993, 91:2744-53
  8. Christiane Y, Aghayan M, Emonard H et.al. Galactose alpha 1-3 galactose and anti-alpha galactose antibody in normal and pathological pregnancies. Placenta 1992, 13:475-87
  9. Sheppard BL, Bonnar J: Uteroplacental hemostasis in intrauterine fetal growth retardation. Semin Thromb Hemost 1999, 25:443-6
  10. Feinberg RF, Kliman HJ, Cohen AW: Preeclampsia, trisomy 13, and the placental bed. Obstet Gynecol 1991, 78:505-8
  11. Kliman HJ: Trophoblast infiltration. Reproductive Medicine Reviews 1994, 3:137-57
  12. Kliman HJ: Trophoblast to human placenta. Encyclopedia of Reproduction, vol 4. Edited by Knobil E, Neill JD. San Diego, Academic Press, 1999, pp 834-46
  13. Kliman HJ, Feinberg RF: Trophoblast differentiation. The First Twelve Weeks of Gestation. Edited by Barnea E, Hustin J, Jauniaux E. New York, Springer-Verlag, 1992
  14. Brown MA, Wang J, Whitworth JA: The renin-angiotensin-aldosterone system in pre-eclampsia. Clin Exp Hypertens 1997, 19:713-26
  15. Gerretsen G, Huisjes HJ, Elema JD: Morphological changes of the spiral arteries in the placental bed in relation to pre-eclampsia and fetal growth retardation. Br J Obstet Gynaecol 1981, 88:876-81
  16. Naeye RL: Pregnancy hypertension, placental evidences of low uteroplacental blood flow, and spontaneous premature delivery.  Hum Pathol 1989, 20:441-4
  17. Soma H, Yoshida K, Mukaida T, Tabuchi Y: Morphologic changes in the hypertensive placenta. Contrib Gynecol Obstet 1982, 9:58-75
  18. Naeye RL: Placental infarction leading to fetal or neonatal death. A prospective study. Obstet Gynecol 1977, 50:583-8