Effects of Intrauterine Growth Restriction and Intraamniotic Insulin-like Growth Factor-I Treatment on Blood and Amniotic Fluid Concentrations and on Fetal Gut Uptake of Amino Acids in Late-Gestation Ovine Fetuses

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Abstract
To investigate, in the late-gestation ovine fetus: 1) amino acid concentrations in blood and amniotic fluid, 2) the effects of intrauterine growth restriction (IUGR) induced by placental embolization on these concentrations, 3) fetal gut uptake of glutamine in healthy and IUGR fetuses, and 4) the effects of intraamniotic insulin-like growth factor-I (IGF-1) treatment on these parameters. Fetuses were randomly assigned to control (n = 9), IUGR + saline (n = 9), or IUGR + IGF-1 (n = 11) groups. IUGR was induced by uteroplacental embolization from 114 to 119 days (term = 145 days). IUGR fetuses received daily intraamniotic injections of saline or IGF-1 (20 microg/d) from 120 to 130 days. Baseline amino acid concentration was higher in fetal blood than amniotic fluid for all essential amino acids except lysine and histidine, but was lower for serine, alanine, and methylhistidine. Embolization reduced total amino acid concentration in blood and amniotic fluid by approximately 15%. Concentrations were reduced for serine, glutamine, and methylhistidine in blood and for serine in amniotic fluid, but were increased for glycine, alanine, and asparagine in blood and for alanine in amniotic fluid. Glutamine was taken up by the fetal gut (glutamine:oxygen quotient of 0.65) and citrulline was released by the gut. IGF-1 treatment did not alter amino acid concentration in blood or amniotic fluid, but reduced gut uptake of glutamine from blood and the gut glutamine:oxygen quotient by 15%. Citrulline release was unchanged. These data suggest that amniotic fluid amino acids are not simply filtered from fetal blood and may provide an important pool of nutrients for the fetus. They demonstrate for the first time that glutamine is taken up by the fetal gut. IGF-1 treatment may promote gut utilization of amino acids from the amniotic fluid pool.