Heparin-binding epidermal growth factor (HB-EGF) may improve embryonic development and implantation by increasing vitronectin receptor (integrin alphanubeta3) expression in peri-implantation mouse embryos

PURPOSE: This study investigated the effects of HB-EGF on expression of integrin alphanubeta3 and implantation of embryos. METHODS: Two-cell embryos were recovered and cultured with or without 10 ng/mL HB-EGF for 96h. Expression of integrin alphanubeta3 in cultured embryos was examined by real time-RT-PCR and immunofluorescence analysis; embryos were cultured with or without HB-EGF, then transferred into the uteri of pseudo-pregnant female mice in order to analyze their implantation rate. RESULTS: HB-EGF improved embryonic hatching and outgrowth during extended culture, and up-regulated expression of integrin alphanubeta3 in both the preimplantation embryo and outgrowing blastocyst. Also, integrin alphanubeta3 subunits were localized at the pericellular borders and cell-cell contact areas. The number of successful implantation sites of transferred HB-EGF-treated embryos in the uterus was increased when compared to number of implantation sites with non-treated controls. CONCLUSIONS: HB-EGF may improve implantation by accelerating expression of integrin alphanubeta3 in peri-implantation mouse embryos.