Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases fetal amino acid oxidation

Paul J. Rozance, Michelle M. Crispo, James S. Barry, Meghan C. O'Meara, Mackenzie S. Frost, Kent C. Hansen, William W. Hay, Laura D. Brown

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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 μmol·min -1·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 μmol·min-1·kg-1, P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 ± 23 vs. 250 ± 29 μmol·min-1·kg-1, P = 0.06). Rates of leucine incorporation into fetal protein (5.19 ± 0.97 vs. 5.47 ± 0.89 μmol·min-1·kg-1, AA vs. C), release from protein breakdown (4.20 ± 0.95 vs. 4.62 ± 0.74 μmol·min-1·kg-1), and protein accretion (1.00 ± 0.30 vs. 0.85 ± 0.25 μmol·min -1·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, eIF2α, and p70S6K. 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.

Original languageEnglish (US)
Pages (from-to)E638-E646
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume297
Issue number3
DOIs
StatePublished - Sep 1 2009

Keywords

  • Leucine
  • Metabolism
  • Oxygen
  • Threonine

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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