Maternal insulin-like growth factors-I and -II act via different pathways to promote fetal growth.
The placenta transports substrates and wastes between the maternal and fetal circulations. In mice, placental 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.d), or vehicle sc from d 20-38 of pregnancy and killed on d 62 (term = 69 d). IGF-II, but not IGF-I, increased the mid-sagittal area and volume of placenta devoted to exchange by approximately 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 approximately 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, whereas 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.
Research Center for Reproductive Health, Discipline of Obstetrics and Gynecology, University of Adelaide, Adelaide, South Australia, Australia 5005.
Amanda N
AN
Sferruzzi-Perri
Julie A
JA
Owens
Kirsty G
KG
Pringle
Jeffrey S
JS
Robinson
Claire T
CT
Roberts
D000818:Animals; D005260:Female; D047109:Fetal Development; D006168:Guinea Pigs; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D009035:Mothers; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal; D014327:Trophoblasts / Q000378:metabolism
D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II