Selective insulin-like growth factor-I antagonist inhibits mouse embryo development in a dose-dependent manner

Objective: To study the role of a synthetic insulin-like growth factor-I receptor (IGF-IR) antagonist, picropodophyllin, for mouse preimplantation embryo development in vivo and in vitro. Design: In vitro and in vivo study. Setting: Hospital-based research unit. Animals: FVB/N mice and mouse embryos. Intervention(s): The effect of picropodophyllin in mouse embryo development in vivo and in vitro, immunohistochemistry, ELISA, polymerase chain reaction. Main Outcome Measure(s): Embryo development, presence of IGF-IR, messenger RNA expression, IGF-I synthesis. Result(s): The effect of picropodophyllin on embryo development in vitro and in vivo was not reversible. Mice treated with picropodophyllin 1 to 3 days after mating had a reduced number of blastocysts, 40.5% versus 78.8%, and a higher number of embryos with delayed development, 48.6% versus 11.5%. Insulin-like growth factor-IR protein is present in both phosphorylated and nonphosphorylated form at all stages of embryo development. The relative IGF-IR messenger RNA expression was highest in the oocyte and reduced during development to blastocyst stage. Insulin-like growth factor-I in culture media was reduced after picropodophyllin treatment. Conclusion(s): We conclude that IGF-I has an important role in normal mouse embryo development and that its receptor plays an essential role in the embryonic genome activation process. (Fertil Steril (R) 2010; 93: 2621-6. (C) 2010 by American Society for Reproductive Medicine.)