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Selective insulin-like growth factor-I antagonist inhibits mouse embryo development in a dose-dependent manner
Jose Inzunza1, Olle Danielsson, Parameswaran Grace Lalitkumar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
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.
Insights
Insulin-like growth factor-I (IGF-I) is crucial for mouse embryo development. Blocking its receptor with picropodophyllin impairs embryo development and blastocyst formation, highlighting IGF-I
Area of Science:
- Reproductive biology
- Developmental biology
- Molecular endocrinology
Background:
- Insulin-like growth factor-I (IGF-I) signaling is vital for mammalian development.
- The role of IGF-I and its receptor (IGF-IR) in early embryonic development requires further elucidation.
- Picropodophyllin is a synthetic IGF-IR antagonist.
Purpose of the Study:
- To investigate the impact of picropodophyllin, an IGF-IR antagonist, on mouse preimplantation embryo development.
- To assess the effects of picropodophyllin on embryo development both in vivo and in vitro.
Main Methods:
- In vitro and in vivo studies using FVB/N mice and their embryos.
- Treatment with picropodophyllin to inhibit IGF-IR.
- Analysis of embryo development, IGF-IR presence, mRNA expression, and IGF-I synthesis using immunohistochemistry, ELISA, and PCR.
Main Results:
- Picropodophyllin treatment significantly reduced blastocyst formation rates (40.5% vs. 78.8%) and increased developmental delays (48.6% vs. 11.5%) in vivo.
- IGF-IR protein was detected at all embryonic stages, with highest relative mRNA expression in oocytes, decreasing towards the blastocyst stage.
- IGF-I levels in culture media were reduced following picropodophyllin treatment, indicating impaired IGF-I synthesis or signaling.
Conclusions:
- IGF-I plays a critical role in normal mouse preimplantation embryo development.
- The IGF-IR is essential for embryonic genome activation during early development.
- Inhibition of IGF-IR signaling by picropodophyllin has detrimental and irreversible effects on embryo development.
