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.

Key Words: Picropodophyllin, PPP, embryo, development