Effects of Human Endothelial Progenitor Cell and Its Conditioned Medium on Oocyte Development and Subsequent Embryo Development

Human endothelial progenitor cells (EPCs) secrete numerous growth factors, and they have been applied to regenerative medicine for their roles in angiogenesis as well as neovascularization. Angiogenesis is one of the essential factors for the maturation of ovarian follicles; however, the physiological function of EPCs or their derivatives on in vitro culture systems has not been fully understood. The aim of this study was to evaluate the effectiveness of EPCs and their conditioned medium (EPC-CM) on oocyte development and subsequent embryo development. In the results, the oocyte development and subsequent embryo development were significantly improved in EPCs and the EPC-CM group. In addition, markedly increased levels of growth factors/cytokines, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin growth factor-1 (IGF-1), interleukin-10 (IL-10), and epidermal growth factor (EGF), were observed in medium from the EPC-CM group. Additionally, EPC-CM after in vitro maturation (IVM) had significantly decreased reactive oxygen species (ROS) levels compared to those of other groups. Transcriptional levels of growth factor receptor-related genes (FGFR2, IGF1R) and anti-apoptotic-related gene (BCL2) were significantly upregulated in cumulus cells/oocytes from the EPC-CM group compared with those from the control. Furthermore, the expression levels of cumulus expansion-related genes (PTGS2, TNFAIP6, HAS2) and oocyte-maturation-related factors (GDF9, BMP15) were significantly enhanced in the EPC-CM group. Consequently, the present study provides the first evidence that EPC-CM contains several essential growth factors for oocyte development by regulating genes involved in oocyte maturation.