title: In vitro migration of cytotrophoblasts through a decidual endothelial cell monolayer: the role of matrix metalloproteinases.
abstract: Deficient trophoblast invasion is a major feature of pre-eclampsia. In vitro studies suggest that in normal pregnancy, maternal cells may play a role in controlling trophoblast invasion, although the exact nature of the regulatory interactions between these cells is not fully understood. To examine the effect of maternal-placental cell interactions on matrix metalloproteinase (MMP) secretion and endovascular cytotrophoblast migration in normal pregnancy and in pre-eclampsia, we performed co-culture experiments using cytotrophoblasts from normal pregnancies, together with decidual endothelial cells from both normal and preeclamptic pregnancies. Cells were incubated on semi-permeable membranes with or without phorbol 12-myristate 13-acetate (PMA). Results showed that third trimester cytotrophoblasts are migratory under basal conditions and display a different MMP profile from decidual endothelial cells. Co-culture did not damage either cell type and resulted in reduced latent MMP-9 secretion and reduced cytotrophoblast migration. Although PMA upregulated MMPs in decidual endothelial cells, it had no effect on cytotrophoblast MMP secretion. PMA, however, reduced cytotrophoblast migration. Pre-eclamptic decidual endothelial cells showed reduced MMP-1 secretion, but overall were not different in co-culture from normal endothelial cells. This study demonstrates the effectiveness of a bilayer co-culture model to study maternal-foetal cell interactions and provides evidence that maternal cells may contribute to the control of endovascular cytotrophoblast invasion.
authors.affiliation: Department of Renal Medicine, Kolling Institute of Medical Research, Sydney, Australia. gjb2@cam.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Campbell
authors.forename: J
authors.initials: J
authors.lastname: Rowe
authors.forename: C J
authors.initials: CJ
authors.lastname: Jackson
authors.forename: E D M
authors.initials: ED
authors.lastname: Gallery
mesh_terms: D000328:Adult; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D003656:Decidua / Q000187:drug effects / Q000502:physiology*; D010064:Embryo Implantation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D020782:Matrix Metalloproteinases; D013755:Tetradecanoylphorbol Acetate