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.


METHODS
In vitro and in vivo study.


METHODS
Hospital-based research unit.


METHODS
FVB/N mice and mouse embryos.


METHODS
The effect of picropodophyllin in mouse embryo development in vivo and in vitro, immunohistochemistry, ELISA, polymerase chain reaction.


METHODS
Embryo development, presence of IGF-IR, messenger RNA expression, IGF-I synthesis.


RESULTS
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.


CONCLUSIONS
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.
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Jose
J
Inzunza
Olle
O
Danielsson
Parameswaran Grace
PG
Lalitkumar
Olle
O
Larsson
Magnus
M
Axelson
Virpi
V
Töhönen
Kristina Gemzell
KG
Danielsson
Anneli
A
Stavreus-Evers
D000818:Animals; D047108:Embryonic Development / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism
D012333:RNA, Messenger; C415032:picropodophyllin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin