Selective insulin-like growth factor-I antagonist inhibits mouse embryo development in a dose-dependent manner
Received 30 September 2009; received in revised form 14 December 2009; accepted 16 December 2009. published online 05 February 2010. Corrected Proof
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.
aDepartment of Biosciences and Nutrition, Karolinska Institutet, Stockholm
bDepartment of Laboratory Medicine, Karolinska Institutet, Stockholm
cDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm
dDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm
eDepartment of Women's and Children's Health, Uppsala University, Uppsala, Sweden
Reprint requests: Anneli Stavreus-Evers, Ph.D., Department of Women's and Children's Health, Uppsala University, Uppsala University Hospital, SE-751 85 Uppsala, Sweden (FAX: 46-18-559-775).
J.I. has nothing to disclose. O.D. has nothing to disclose. P.G.L. has nothing to disclose. O.L. has nothing to disclose. M.A. has nothing to disclose. V.T. has nothing to disclose. K.G.D. has nothing to disclose. A.S.-E. has nothing to disclose.
Supported by grants from the Swedish Scientific Council (2005-7293), Karolinska Institutet, Stockholm County Council, Åke Wibergs foundation, and Goljes Foundation.
Dr. Kristina Gemzell Danielsson and Dr. Anneli Stavreus-Evers contributed equally to this work.
ABSTRACT