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Journal of the Society for Gynecologic Investigation, Vol. 13, No. 1, 40-47 (2006)
DOI: 10.1016/j.jsgi.2005.09.010

An Imbalance Between Vascular Endothelial Growth Factor and its Soluble Receptor in Placental Villous Explants of Intrauterine Growth-Restricted Pregnancies

Sudha Padavala, MBBS

Nicole Pope, MBBS

Philip Beker, DM

Maternal and Fetal Health Research Centre, St. Mary's Hospital, Manchester, United Kingdom; The Royal Hallamshire Hospital, Sheffield, United Kingdom

Ian Crocker, PhD

Maternal and Fetal Health Research Centre, St. Mary's Hospital, Manchester, United Kingdom; The Royal Hallamshire Hospital, Sheffield, United Kingdom Ian.Crocker{at}manchester.ac.uk

Objectives: Human umbilical vascular endothelial cells (HUVECs), seeded on Matrigel (BD Biosciences, Bedford, UK), undergo an angiogenic-like process. WE Hypothesized that placental explants from normal pregnancies, maintained in cultures of different oxygen, would liberate factors that could be measured in this system. We furhter tested the angiogenic potential of placentae from intrauterine growth-restricted (IUGR) pregnancies and the effects of vascular endothelial growth factor (VEGF) blockade.

Methods: Placental villos explants were maintained in culture at 3% and 20% O2. The resultant media was added to HUVECs seeded on 80% Matrigel. Cells were incubated at 6% O2 in accordance with the natural placental environment. After 6 hours, cells were fixed and stained and the length and number of tubules measured by morphometric imaging. Finally, VEGF and soluble VEGF receptor (sVEGFR-1) were recorded in the explant conditioned media.

Results: Within the angiogenic assay, recombinant human VEGF significantly enhanced tubule outgrowth (branching and elongation) and this effect was effect was blocked with neutralising antibody. Compare do 20% O2, media of placental explants conditioned at 3% O2 significantly encouraged tubule length and numbers. Again this affect was ablated by VEGF blockade. In cases of IUGR, conditioned media at #% O2 showed a significant reduction in tubule growth. This was paralleled by a decline in available VEGF brought about an exaggeration in liberated sVEGRF-1. Notably, venous cord serum from IUGR pregnancies showed a similar elevation in sVEGGR-1.

Conclusion: Under restricted oxygen, placental angiogenic potential is suppressed in IUGR pregnancies through the overproduction of placental sVEGFR-1. This reduction may discourage normal placental vascularization and impact on fetal development.

Key Words: Placenta • angiogenesis • intrauterine growth restriction • vascular endothelial growth factor • soluble vascular endothelial grtowh factor receptor


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