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Session XVII : Cell signaling in health and disease Poster XVII, 38
HYPOXIA IS RESPONSIBLE OF sVEGF-R1 INDUCTION IN VILLOUS
TROPHOBLAST EXPLANTS CULTURE
Carine Munaut , Sarah Berndt , Sophie Lorquet, Christel Pequeux, Francis Frankenne,
Van den Brûle Frédérique and Jean-Michel Foidart.
Laboratory of Tumor and Development Biology, CRCE, CHU, GIGA, EMBIC partners.
University of Liège, Tour de Pathologie (B23), Sart Tilman, B-4000 Liège, Belgium.
Preeclampsia is a disorder unique to human pregnancy characterized by a generalized
systemic maternal inflammatory response, associated with diffuse endothelial cell
dysfunction. It is one of the leading causes of maternal and perinatal morbidity and mortality,
affecting 5% to 7% of all pregnancies, yet the etiology and pathogenesis have not been fully
defined.
Oxygen plays a central role in this pathology. Recently, preeclampsia has been described as a
state of imbalance between pro-angiogenic and anti-angiogenic factors. Main pro-angiogenic
factors that promote angiogenesis in the placenta belong to VEGF family.
We have previously shown that preeclampsia was associated with low levels of circulating
PlGF and increased levels of total VEGF-A and soluble VEGF-R1 (Tsatsaris et al, 2003,
J.Clin.Endocrinol.Metab). Here, our study was undertaken to test the hypothesis that high
levels of those angiogenic factors could be related to hypoxic status of placenta in
preeclampsia.
Small fragments of placental villi from first trimester (11-14 weeks) voluntary interrupted
pregnancies were used for explant culture under normoxia (20% O2, and 5% CO2) or hypoxia
(1% O2, 5% CO2 and 94% N2). Under hypoxia, villous trophoblast explants expressed higher
levels of VEGF-A, VEGF-R1, sVEGF-R1 and VEGF-R2 mRNAs than under normoxia
culture. By contrast, PlGF mRNA was decreased in hypoxia. Protein secretion of VEGF-A
and sVEGF-R1, determined by ELISA, were also found elevated in hypoxic explant cultures.
No histological or morphological modifications were observed under hypoxia as compared to
normoxia.
Our data show that villous trophoblast is the likely source of increased plasma levels of
VEGF-A and VEGF-R1 in pregnant woman. Our results also support the hypothesis that
overproduction of sVEGF-R1 by villous trophoblast submitted to extended hypoxia in
preeclampsia could account for the depletion of maternal blood free VEGF.
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