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.
Inzunza
Jose
J
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Danielsson
Olle
O
Lalitkumar
Parameswaran Grace
PG
Larsson
Olle
O
Axelson
Magnus
M
Töhönen
Virpi
V
Danielsson
Kristina Gemzell
KG
Stavreus-Evers
Anneli
A
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