Heavy drinking during pregnancy can result in
fetal alcohol syndrome (FAS), of which, fetal and postnatal growth retardation and central nervous system deficits are cardinal features. Although a number of mechanisms have been proposed, none fully account for these deficiencies. We have previously reported that maternal
ethanol exposure (1.75 g/kg) results in transient acidemia in the mother and fetus. Alterations in pH are known to regulate
glutamine homeostasis. Therefore, we hypothesized that chronic binge
ethanol-mediated
acidosis reduces
glutamine concentrations in maternal plasma that result in decreases in the circulating levels of
amino acids related to
glutamine metabolism. Pregnant ewes were divided into three groups:
ethanol (1.75 g/kg), saline control, and acidemia (inspired fractional
carbon dioxide [CO(2)] was manipulated to mimic the maternal arterial pH pattern created by
ethanol). The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109, continuing to GD 132. Plasma samples were analyzed for nutrients and metabolites using HPLC and spectrophotometric methods. Maternal plasma concentrations of
glutamate increased (58%), whereas
glutamine,
citrulline, and
arginine decreased (between 14 and 53%) in response to an acute challenge after the chronic exposure in
ethanol-treated ewes. No differences in these
amino acid concentrations were noted between the
ethanol and acidemic group subjects. Maternal plasma
lactate levels increased by approximately 100% in response to
ethanol, whereas
glucose and
urea levels did not change in any group. We conclude that maternal chronic binge
ethanol consumption results in
acidosis-mediated reductions in circulating levels of
glutamine and related
amino acids that could be responsible for neuronal deficits, altered fetal growth, development, and programming. We also speculate that the consequent increase in fetal
glutamate during critical periods of brain development may contribute to the pathogenesis of FAS.