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Mol. Hum. Reprod. Advance Access originally published online on May 4, 2006
Molecular Human Reproduction 2006 12(6):389-399; doi:10.1093/molehr/gal044
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associatedwith pre-eclampsia

Alexandra Gellhaus1, Markus Schmidt2, Caroline Dunk3, Stephen J. Lye3, Rainer Kimmig2 and Elke Winterhager1,4

1Institute of Anatomy and 2Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany and 3Department of Obstetrics and Gynecology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

4 To whom correspondence should be addressed at: Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. E-mail: e.winterhager{at}uni-essen.de

The pregnancy disorder pre-eclampsia (PE) is thought to be caused in part by shallow invasion of the extravillous trophoblast (EVT) leading to uteroplacental insufficiency and hypoxia. Here, we focused on the expressions of cysteine-rich 61 (CYR61, CCN1) and nephroblastoma overexpressed (NOV, CCN3), members of the CCN family of angiogenic regulators, in human placenta during normal pregnancy compared with pre-eclamptic and HELLP placentae using quantitative RT–PCR, western blotting and immunocytochemistry. During normal pregnancy, both proteins showed increasing expression levels and were strongly coexpressed in endothelial cells of vessels, stromal cells and interstitial EVT giant cells. However, NOV showed an earlier onset of expression in villous endothelial cells during gestation compared with CYR61, which may signify distinct roles of these proteins in placental angiogenesis. In early-onset pre-eclamptic placentae, both CYR61 and NOV were expressed at a significantly lower level compared with normal matched controls. This decrease of CYR61 and NOV in pre-eclamptic placentae is not associated with a decrease of the endothelial marker CD34 or vimentin. No obvious changes in the localization of CYR61 and NOV in pre-eclamptic placentae were detected but a change in the intracellular distribution in trophoblast giant cells. Our data point to a potential role of both molecules in the pathogenesis of early-onset PE.

Key words: angiogenesis/CCN/CYR61/NOV/placenta/pre-eclampsia


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A. Gellhaus, M. Schmidt, C. Dunk, S. J. Lye, and E. Winterhager
The Circulating Proangiogenic Factors CYR61 (CCN1) and NOV (CCN3) Are Significantly Decreased in Placentae and Sera of Preeclamptic Patients
Reproductive Sciences, December 1, 2007; 14(8_suppl): 46 - 52.
[Abstract] [PDF]


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