Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases fetal amino acid oxidation.
Protein supplementation during human pregnancy does not improve fetal growth and may increase small-for-gestational-age birth rates and mortality. To define possible mechanisms, sheep with twin pregnancies were infused with amino acids (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA group, fetal arterial pH (7.365 +/- 0.007 day 0 vs. 7.336 +/- 0.012 day 4, P < 0.005), hemoglobin-oxygen saturation (46.2 +/- 2.6 vs. 37.8 +/- 3.6%, P < 0.005), and total oxygen content (3.17 +/- 0.17 vs. 2.49 +/- 0.20 mmol/l, P < 0.0001) were decreased on day 4 compared with day 0. Fetal leucine disposal did not change (9.22 +/- 0.73 vs. 8.09 +/- 0.63 micromol x min(-1) x kg(-1), AA vs. C), but the rate of leucine oxidation increased 43% in the AA group (2.63 +/- 0.16 vs. 1.84 +/- 0.24 micromol x min(-1) x kg(-1), P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 +/- 23 vs. 250 +/- 29 micromol x min(-1) x kg(-1), P = 0.06). Rates of leucine incorporation into fetal protein (5.19 +/- 0.97 vs. 5.47 +/- 0.89 micromol x min(-1) x kg(-1), AA vs. C), release from protein breakdown (4.20 +/- 0.95 vs. 4.62 +/- 0.74 micromol x min(-1) x kg(-1)), and protein accretion (1.00 +/- 0.30 vs. 0.85 +/- 0.25 micromol x min(-1) x kg(-1)) did not change. Consistent with these data, there was no change in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein synthesis regulators 4E-BP1, eEF2, eIF2alpha, and p70(S6K). Decreased concentrations of certain essential amino acids, increased amino acid oxidation, fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal toxicity during maternal amino acid supplementation.
Rozance
Paul J
PJ
Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
Crispo
Michelle M
MM
Barry
James S
JS
O'Meara
Meghan C
MC
Frost
Mackenzie S
MS
Hansen
Kent C
KC
Hay
William W
WW
Brown
Laura D
LD
D000465:Algorithms; D000596:Amino Acids / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism*; D005865:Gestational Age; D007260:Infusion Pumps; D019344:Lactic Acid / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D011247:Pregnancy; D011897:Random Allocation; D012756:Sheep; D013997:Time Factors
D000596:Amino Acids; D001786:Blood Glucose; D019344:Lactic Acid