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This version published online on March 23, 2006
Endocrinology, doi:10.1210/en.2005-1328
A more recent version of this article appeared on July 1, 2006
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*Substance via MeSH

Submitted on October 19, 2005
Accepted on March 16, 2006

Maternal insulin-like growth factors-I and -II act via different pathways to promote fetal growth

Amanda N. Sferruzzi-Perri, Julie A. Owens, Kirsty G. Pringle, Jeffrey S. Robinson, and Claire T. Roberts*

Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, South Australia, Australia, 5005

* To whom correspondence should be addressed. E-mail: claire.roberts{at}adelaide.edu.au.

The placenta transports substrates and wastes between the maternal and fetal circulations. In mice, placental insulin-like growth factor (IGF)-II is essential for normal placental development and function but in other mammalian species maternal circulating IGF-II is substantial and may contribute. Maternal circulating IGFs increase in early pregnancy and early treatment of guinea pigs with either IGF-I or IGF-II increases placental and fetal weights by mid-gestation. We now show that these effects persist to enhance placental development and fetal growth and survival near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg/day) or vehicle subcutaneously from days 20 to 38 of pregnancy and killed on day 62 (term=69 days). IGF-II, but not IGF-I, increased the mid-sagittal area and volume of placenta devoted to exchange by ~30%, the total volume of trophoblast and maternal blood spaces within the placental exchange region (+29% and +46%, respectively) and the total surface area of placenta for exchange by 39%. Both IGFs reduced resorptions and IGF-II increased the number of viable fetuses by 26%. Both IGFs increased fetal weight by 11-17% and fetal circulating amino acid concentrations. IGF-I, but not IGF-II, reduced maternal adipose depot weights by ~30%. In conclusion, increased maternal IGF-II abundance in early pregnancy promotes fetal growth and viability near term by increasing placental structural and functional capacity, while IGF-I appears to divert nutrients from the mother to the conceptus. This suggests major and complementary roles in placental and fetal growth for increased circulating IGFs in early to mid pregnancy.
Key words: IGF-I • IGF-II • placenta • fetal growth




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