The Regulation of Vascular Endothelial Growth Factor Expression by G-CSF in Human Endometrium

Objective. To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on the expression of vascular endothelial growth factor (VEGF) and the transcription factor HOXA10 in primary human endometrial cell cultures. Methods. Eight patients undergoing evaluation prior to assisted reproductive technology (ART) programs were enrolled. Endometrial biopsy was performed on cycle days 5–10. The obtained tissue was cultured for 72 hours in DMEM supplemented with different concentrations of G-CSF (1 and 100 mg/mL). VEGF and HOXA10 expression was assessed by real-time PCR, and VEGF concentration in the culture medium was measured by ELISA. Statistical analysis was performed using ANOVA and Tukey’s test. Results. A dose-dependent stimulatory effect of G-CSF on VEGF (F(2,21)=31.55; p0.001) and HOXA10 (F(2,21)=14.31; p0.001) gene expression was demonstrated. Increased expression was observed already at 1 mg/mL, while statistically significant changes were obtained at 100 mg/mL. VEGF protein concentration in the culture medium was also significantly increased by G-CSF (F(2,21)=109.4; p0.001). The stimulatory effect was consistent across all examined endometrial samples. Conclusions. G-CSF exerts a pleiotropic effect by upregulating VEGF and HOXA10 expression in endometrial cells in vitro. These mechanisms may underlie endometrial regeneration and improved receptivity, supporting its therapeutic potential in patients with refractory endometrium and repeated implantation failure in ART programs.