IGF-1 infusion to fetal sheep increases organ growth but not by stimulating nutrient transfer to the fetus

Am J Physiol Endocrinol Metab. 2021 Mar 1;320(3):E527-E538. doi: 10.1152/ajpendo.00453.2020. Epub 2021 Jan 11.


Insulin-like growth factor-1 (IGF-1) is an important fetal growth factor. However, the role of fetal IGF-1 in increasing placental blood flow, nutrient transfer, and nutrient availability to support fetal growth and protein accretion is not well understood. Catheterized fetuses from late gestation pregnant sheep received an intravenous infusion of LR3 IGF-1 (LR3 IGF-1; n = 8) or saline (SAL; n = 8) for 1 wk. Sheep then underwent a metabolic study to measure uterine and umbilical blood flow, nutrient uptake rates, and fetal protein kinetic rates. By the end of the infusion, fetal weights were not statistically different between groups (SAL: 3.260 ± 0.211 kg, LR3 IGF-1: 3.682 ± 0.183; P = 0.15). Fetal heart, adrenal gland, and spleen weights were higher (P < 0.05), and insulin was lower in LR3 IGF-1 (P < 0.05). Uterine and umbilical blood flow and umbilical uptake rates of glucose, lactate, and oxygen were similar between groups. Umbilical amino acid uptake rates were lower in LR3 IGF-1 (P < 0.05) as were fetal concentrations of multiple amino acids. Fetal protein kinetic rates were similar. LR3 IGF-1 skeletal muscle had higher myoblast proliferation (P < 0.05). In summary, LR3 IGF-1 infusion for 1 wk into late gestation fetal sheep increased the weight of some fetal organs. However, because umbilical amino acid uptake rates and fetal plasma amino acid concentrations were lower in the LR3 IGF-1 group, we speculate that animals treated with LR3 IGF-1 can efficiently utilize available nutrients to support organ-specific growth in the fetus rather than by stimulating placental blood flow or nutrient transfer to the fetus.NEW & NOTEWORTHY After a 1-wk infusion of LR3 IGF-1, late gestation fetal sheep had lower umbilical uptake rates of amino acids, lower fetal arterial amino acid and insulin concentrations, and lower fetal oxygen content; however, LR-3 IGF-1-treated fetuses were still able to effectively utilize the available nutrients and oxygen to support organ growth and myoblast proliferation.

Keywords: amino acids; fetal growth; umbilical substrate uptake; uterine substrate uptake.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Energy Metabolism / drug effects
  • Female
  • Fetal Blood / metabolism
  • Fetal Development / drug effects*
  • Fetal Weight / drug effects
  • Fetus / drug effects
  • Fetus / metabolism
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • Nutrients / metabolism*
  • Organ Size / drug effects
  • Placenta / drug effects
  • Placentation / drug effects
  • Pregnancy
  • Sheep


  • Insulin-Like Growth Factor I