Sufficient cytotrophoblast (CT) invasion into the uterine wall and subsequent remodeling of maternal uterine vasculature is critical to establish uteroplacental circulation. The production of
vascular endothelial growth factor (
VEGF) family molecules is confirmed in placental cells including CTs, but it is not elucidated how the
VEGF system in CTs is controlled by
oxygen tension and how it is involved in the development of placental circulation. To address this, we explored the effect of
oxygen tension on the expression of
VEGF,
placenta growth factor (PlGF), and their antagonist, soluble fms-like
tyrosine kinase-1 (sFlt-1) using ELISA and real-time PCR in a primary CT cell culture. For comparison, the same was conducted in parallel using other cells comprising placenta, such as human umbilical vein endothelial cells (HUVECs) and villous fibroblasts (VFs). Reduced
oxygen resulted in a pronounced increase in sFlt-1
mRNA amount and sFlt-1 release into the
culture media in CTs, whereas this was not the case with HUVECs and VFs. Free (not bound to sFlt-1)
VEGF was not detected in CT
culture media regardless of
oxygen concentration, even though
VEGF expression was stimulated by reduced
oxygen in CTs, which was similar to the stimulation in HUVECs and VFs. Free PlGF was also diminished in CT
culture media by reduced
oxygen. These results implicate that CTs possess a unique property to enhance sFlt-1 production under reduced
oxygen, which could consequently antagonize angiogenic activity of
VEGF and PlGF. The presented findings might provide a framework with which to understand the mechanism of uterine
vascular remodeling and its perturbations as exemplified in
preeclampsia.