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. ( J. Clin. Invest. 1997. 99:2152-2164.)

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

“…Notably, immunofluorescence revealed that the particular adhesion molecule specifically localizes to proliferative CCTs in the intermediate region of the cell column (Fig. 5B) (12). Hence, N1ICD-induced VE-cadherin expression might suggest that cell column progenitors have further developed into TA-like cells.…”

“…Besides unfavorable immunological interactions of EVTs with uterine natural killer (uNK) cells (11), abnormal placental development and trophoblast differentiation are thought to contribute to the pathogenesis of gestational disorders. Indeed, CTBs isolated from preeclamptic placentae failed to appropriately differentiate into the invasive lineage in vitro and expressed an antimigratory gene signature (12,13).…”

New Aspects in the Pathophysiology of Preeclampsia

“…In preeclampsia, there is shallow placental cytotrophoblast invasion of uterine spiral arterioles, leading to reduced placental perfusion and consequently placental insufficiency. Both in vitro and in vivo studies show that trophoblasts obtained from patients with preeclampsia fail to undergo these alterations of adhesion molecules and pseudovasculogenesis (15,16). The molecular pathways that regulate pseudovasculogenesis may involve a vast array of transcription factors, growth factors, and cytokines (17).…”

Circulating endothelial cells in preeclampsia

“…1 It is characterized by abnormal vascular response to placentation that is associated with increased systemic vascular resistance, enhanced platelet aggregation, activation of the coagulation system and endothelial cell dysfunction. 2 An initiating event in preeclampsia has been postulated to be reduced placental perfusion that leads to widespread dysfunction of the maternal vascular endothelium.…”