Glucocorticoids inhibit angiogenesis and dysregulate angiogenic factors in the human placenta

Objectives: Fetal growth restriction (FGR) has been linked with excessive exposure to glucocorticoids (GCs) in animal and human pregnancies. In rodents, GC treatment reduces placental angiogenesis and inhibits expression of vascular endothelial growth factor (VEGF). We hypothesized that GCs inhibit angiogenesis in human placenta by dysregulating angiogenic factors.Methods: Human umbilical vein endothelial cells (HUVECs, n=3) and primary human placental arterial endothelial cells (HPAECs, n=7) were treated with hydrocortisone, prednisolone and dexamethasone (10-1,000nM). Tube-like structure (TLS) formation in matrigel and cellular migration following scratching were assessed after 24 and 48h respectively. Cell viability, proliferation and apoptosis were assessed by MTT, APO% and LDH assays. Additional angiogenesis assays were conducted in the presence of angiogeneic factors (VEGF-A, FGF-2 and IL-8; 10nM). Chorionic plate arteries (CPA) from term placentas (n=10) and first trimester villous tissue were cultured for 48h with GCs (1000nM). mRNA expression of angiogenic regulators was quantified by Q-PCR.Results: All three GCs dose-dependently reduced TLS formation in HUVECs and HPAECs (to 20-30% of vehicle, p