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Interaction of Cocultured Decidual Endothelial Cells and Cytotrophoblasts in Preeclampsia¹

Perinatal Research Group,³ Kolling Institute of Medical Research Sutton Arthritis Research Laboratory,⁴ Institute of Bone and Joint Research, The University of Sydney at Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia

Disturbed cell-cell communication between trophoblasts and the maternal endothelium may be responsible for the deficient endovascular invasion seen in preeclampsia. In vitro studies have been hampered by lack of suitable models to directly examine interactions between these cell types. Using a bilayer coculture model, we examined the effect of decidual endothelial cells on matrix metalloproteinase secretion and the migration of cytotrophoblasts from preeclamptic pregnancies. Cells were incubated on semipermeable membranes in 20% or 2% O₂ with or without the tumor promoter phorbol 12-myristate 13-acetate, which activates matrix metalloproteinase-2 and -9 in endothelial cells. Cytotrophoblasts from preeclamptic pregnancies secreted significantly less matrix metalloproteinase-2 and -9 than their normal counterparts. Although decidual endothelial cells downregulated cytotrophoblast migration in normal pregnancy, this was not observed in cocultures with cytotrophoblasts from preeclamptic pregnancies. In addition, cytotrophoblasts from preeclamptic pregnancies altered phorbol myristate acetate-induced activation of endothelial matrix metalloproteinases. Hypoxia increased cytotrophoblast migration when cells were incubated alone but not in coculture with decidual endothelial cells due to increased adhesion between the two cell types. These results suggest dysfunctional interactive regulation of migration and matrix metalloproteinase secretion in preeclampsia that could result in abnormal endovascular trophoblast invasion of the maternal vasculature.

¹ Supported by a Project Grant and Postgraduate Biomedical Research Scholarship from the National Health and Medical Research Council of Australia and a Royal North Shore Hospital Centenary Foundation Postgraduate Scholarship.

² Correspondence: E.D.M. Gallery, Department of Renal Medicine, The University of Sydney at Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. FAX: 612 9436 3719; eileeng{at}med.usyd.edu.au

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