Endometrial decidual stromal cell-derived sEVs miR-27b-3p promotes angiogenesis via the SPRY2/HGF signaling pathway

Decidualization and the formation of vascular networks is crucial for successful embryo implantation, placentation, and embryo development. However, the relationship between decidual stromal cell and angiogenesis remains poorly understood. In the present study, we aimed to demonstrate the influence and underlying mechanism of decidual stromal cell-derived small extracellular vesicles(sEVs) on angiogenesis. The results revealed that : (1) the enrichment of miRNAs from HDSC (human decidual stromal cells) -sEVs (small extracellular vesicles) associated with angiogenesis-related signaling pathways; (2) the entry of HDSC-sEVs into HUVECs(human umbilical vein endothelial cells) occurs in a time- and dose-dependent manner, which is facilitated by macropinocytosis and clathrin-mediated endocytosis; (3) HDSC-sEVs enhanced the proliferation, invasion, migration, and tube-forming ability of HUVECs. Co-culture of HDSC-sEVs with HUVECs resulted in a significant upregulation of miR-27b-3p and downregulation of SPRY2 (sprouty RTK signaling antagonist 2), a negative regulator of HGF (hepatocyte growth factor) signaling pathway, which promotes angiogenesis. In conclusion, our study suggests that decidual stromal cell-derived sEVs promote angiogenesis by delivering miR-27b-3p into HUVECs, which downregulates the expression of SPRY2, an HGF inhibitor.