Maternal insulin-like growth factor-II promotes placental functional development via the type 2 IGF receptor in the guinea pig.
In guinea pigs, maternal insulin-like growth factor (IGF) infusion in early-pregnancy enhances placental transport near-term, increasing fetal growth and survival. The effects of IGF-II, but not IGF-I, appear due to enhanced placental labyrinthine (exchange) development. To determine if the type-2 IGF receptor (IGF2R) mediates these distinct actions of exogenous IGF-II in the mother, we compared the impact of IGF-II with an IGF-II analogue, Leu(27)-IGF-II, which only binds the IGF2R. IGF-II, Leu(27)-IGF-II (1mg/kg per day.sc) or vehicle were infused from days 20-38 of pregnancy (term = 67 days) and placental structure and uptake and transfer of [(3)H]-methyl-D-glucose (MG) and [(14)C]-amino-isobutyric acid (AIB) and fetal growth and plasma metabolites, were measured on day 62. Both IGF-II and Leu(27)-IGF-II increased the volume of placental labyrinth, trophoblast and maternal blood space within the labyrinth and total surface area of trophoblast for exchange, compared to vehicle. Leu(27)-IGF-II also reduced the barrier to diffusion (trophoblast thickness) compared to vehicle and IGF-II. Both IGF-II and Leu(27)-IGF-II increased fetal plasma amino acid concentrations and placental transfer of MG to the fetus compared to vehicle, with Leu(27)-IGF-II also increasing AIB transport compared with vehicle and IGF-II. In addition, Leu(27)-IGF-II increased fetal weight compared to vehicle. In conclusion, maternal treatment with IGF-II or Leu(27)-IGF-II in early gestation, induce similar placental and fetal outcomes near term. This suggests that maternal IGF-II in early gestation acts in part via the IGF2R to persistently enhance placental functional development and nutrient delivery and promote fetal growth.
Sferruzzi-Perri
A N
AN
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia 5005, Australia.
Owens
J A
JA
Standen
P
P
Roberts
C T
CT
D019325:3-O-Methylglucose / Q000097:blood / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000596:Amino Acids / Q000097:blood; D000621:Aminoisobutyric Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001808:Blood Vessels / Q000033:anatomy & histology / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007335:Insulin-Like Growth Factor II / Q000031:analogs & derivatives / Q000494:pharmacology*; D008098:Litter Size / Q000187:drug effects; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D017527:Receptor, IGF Type 2 / Q000502:physiology*; D014327:Trophoblasts / Q000187:drug effects
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D017527:Receptor, IGF Type 2; D019325:3-O-Methylglucose; D007335:Insulin-Like Growth Factor II