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J Clin Invest. May 1, 1997; 99(9): 2152–2164.
PMCID: PMC508045

Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome?

Abstract

In human pregnancy, placental cytotrophoblasts that invade the uterus downregulate the expression of adhesion receptors that are characteristic of their epithelial origin, and upregulate the expression of adhesion receptors that are expressed by vascular cells. We suggest that this transformation could be critical to endovascular invasion, the process whereby cytotrophoblasts invade the uterine spiral arterioles and line their walls (Zhou et al. J. Clin. Invest. 1997. 99: 2139-2151.). To better understand the in vivo significance of these findings, we tested the hypothesis that in preeclampsia, an important disease of pregnancy in which endovascular invasion is abrogated, cytotrophoblasts fail to adopt a vascular adhesion phenotype. In experiments described here we stained placental bed biopsy specimens from age-matched control pregnancies and from those complicated by preeclampsia with antibodies that recognize adhesion molecules that are normally modulated during this transformation. In preeclampsia, differentiating/invading cytotrophoblasts fail to express properly many of these molecules, including integrin, cadherin, and Ig superfamily members. These results suggest that preeclampsia is associated with failure of cytotrophoblasts to mimic a vascular adhesion phenotype. The functional consequences of this abnormality are unknown, but are likely to affect negatively cytotrophoblast endovascular invasion and uterine arteriole remodeling, thereby compromising blood flow to the maternal-fetal interface.

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Selected References

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  • Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989 Nov;161(5):1200–1204. [PubMed]
  • Berg CJ, Atrash HK, Koonin LM, Tucker M. Pregnancy-related mortality in the United States, 1987-1990. Obstet Gynecol. 1996 Aug;88(2):161–167. [PubMed]
  • Redman CW. Platelets and the beginnings of preeclampsia. N Engl J Med. 1990 Aug 16;323(7):478–480. [PubMed]
  • CHUN D, BRAGA C, CHOW C, LOK L. CLINICAL OBSERVATIONS ON SOME ASPECTS OF HYDATIDIFORM MOLES. J Obstet Gynaecol Br Commonw. 1964 Apr;71:180–184. [PubMed]
  • Brosens IA, Robertson WB, Dixon HG. The role of the spiral arteries in the pathogenesis of preeclampsia. Obstet Gynecol Annu. 1972;1:177–191. [PubMed]
  • 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 Sep;88(9):876–881. [PubMed]
  • Khong TY, De Wolf F, Robertson WB, Brosens I. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol. 1986 Oct;93(10):1049–1059. [PubMed]
  • Zhou Y, Damsky CH, Chiu K, Roberts JM, Fisher SJ. Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts. J Clin Invest. 1993 Mar;91(3):950–960. [PMC free article] [PubMed]
  • Harrington K, Campbell S. Doppler ultrasound in prenatal prediction and diagnosis. Curr Opin Obstet Gynecol. 1992 Apr;4(2):264–272. [PubMed]
  • Damsky CH, Fitzgerald ML, Fisher SJ. 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. 1992 Jan;89(1):210–222. [PMC free article] [PubMed]
  • Librach CL, Werb Z, Fitzgerald ML, Chiu K, Corwin NM, Esteves RA, Grobelny D, Galardy R, Damsky CH, Fisher SJ. 92-kD type IV collagenase mediates invasion of human cytotrophoblasts. J Cell Biol. 1991 Apr;113(2):437–449. [PMC free article] [PubMed]
  • Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990 Apr 13;248(4952):220–223. [PubMed]
  • McMaster MT, Librach CL, Zhou Y, Lim KH, Janatpour MJ, DeMars R, Kovats S, Damsky C, Fisher SJ. Human placental HLA-G expression is restricted to differentiated cytotrophoblasts. J Immunol. 1995 Apr 15;154(8):3771–3778. [PubMed]
  • Redline RW, Patterson P. Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. Hum Pathol. 1995 Jun;26(6):594–600. [PubMed]
  • Genbacev O, Joslin R, Damsky CH, Polliotti BM, Fisher SJ. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest. 1996 Jan 15;97(2):540–550. [PMC free article] [PubMed]
  • Zhou Y, Fisher SJ, Janatpour M, Genbacev O, Dejana E, Wheelock M, Damsky CH. Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion? J Clin Invest. 1997 May 1;99(9):2139–2151. [PMC free article] [PubMed]
  • Chesley LC. Diagnosis of preeclampsia. Obstet Gynecol. 1985 Mar;65(3):423–425. [PubMed]
  • Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol. 1990 Feb;162(2):311–316. [PubMed]
  • Breuss JM, Gallo J, DeLisser HM, Klimanskaya IV, Folkesson HG, Pittet JF, Nishimura SL, Aldape K, Landers DV, Carpenter W, et al. Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci. 1995 Jun;108(Pt 6):2241–2251. [PubMed]
  • Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994 Apr 22;264(5158):569–571. [PubMed]
  • Birchmeier W. E-cadherin as a tumor (invasion) suppressor gene. Bioessays. 1995 Feb;17(2):97–99. [PubMed]
  • Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood. 1994 Oct 1;84(7):2068–2101. [PubMed]
  • Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, Imhof BA. CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol. 1995 Jul;130(2):451–460. [PMC free article] [PubMed]
  • Hemler ME, Jacobson JG, Brenner MB, Mann D, Strominger JL. VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. Eur J Immunol. 1985 May;15(5):502–508. [PubMed]
  • Belkin VM, Belkin AM, Koteliansky VE. Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development. J Cell Biol. 1990 Nov;111(5 Pt 1):2159–2170. [PMC free article] [PubMed]
  • Gurtner GC, Davis V, Li H, McCoy MJ, Sharpe A, Cybulsky MI. Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation. Genes Dev. 1995 Jan 1;9(1):1–14. [PubMed]
  • Yang JT, Rayburn H, Hynes RO. Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Development. 1995 Feb;121(2):549–560. [PubMed]
  • Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol. 1995;11:73–91. [PubMed]
  • Starkey PM, Sargent IL, Redman CW. Cell populations in human early pregnancy decidua: characterization and isolation of large granular lymphocytes by flow cytometry. Immunology. 1988 Sep;65(1):129–134. [PMC free article] [PubMed]
  • Rosen SD. Cell surface lectins in the immune system. Semin Immunol. 1993 Aug;5(4):237–247. [PubMed]
  • Girard JP, Springer TA. High endothelial venules (HEVs): specialized endothelium for lymphocyte migration. Immunol Today. 1995 Sep;16(9):449–457. [PubMed]
  • Janes SL, Kyle PM, Redman C, Goodall AH. Flow cytometric detection of activated platelets in pregnant women prior to the development of pre-eclampsia. Thromb Haemost. 1995 Oct;74(4):1059–1063. [PubMed]

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