Hypoxia regulates vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 secretion by human oviductal epithelial cells and stromal fibroblasts

ObjectiveTo evaluate the effect of hypoxia on the production of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in the human fallopian tube.DesignThe secretion of VEGF and sFlt-1 by cultured oviductal epithelial cells (OECs) and oviductal stromal fibroblasts (OSFs) in response to hypoxia was investigated.SettingResearch laboratory at a medical school.Patient(s)Normal oviducts obtained from seven premenopausal patients were used.Intervention(s)Oviductal epithelial cells and OSFs were incubated under normoxic (20% O2) or hypoxic (2% O2) conditions.Main Outcome Measure(s)The concentrations of VEGF and sFlt-1 in the culture media of OECs and OSFs were measured by enzyme-linked immunosorbent assays.Result(s)The secretion of both VEGF and sFlt-1 was detected in cultured OECs and OSFs and was found to have been stimulated under hypoxic conditions in these cells.Conclusion(s)The present findings suggest that hypoxia in the local environment may stimulate oviductal vascular permeability by inducing the production of VEGF by oviductal cells. Simultaneous up-regulation of sFlt-1 secretion by these cells under hypoxic conditions may prevent excessive up-regulation of vascular permeability. The modulation of the bias of VEGF and sFlt-1 in the fallopian tubes may contribute to the normal and pathological processes of oviductal fluid secretion by regulating oviductal vascular permeability during the menstrual cycle.