Effect of maternal administration of vigabatrin during late gestation on fetoplacental amino acid profile in the mouse

The objectives were to determine if vigabatrin in late gestation affects fetal growth and causes alterations in amino acid concentrations in the mouse. A single dose of 450 mg/kg VGB in saline or a proportionate volume of saline was administered intraperitoneally (IP) to Theiler outbred (TO) mice on gestation day 15 and maternal plasma, placentae and fetuses were collected at different time intervals after treatment. VGB attained peak concentration in the maternal plasma and the fetus at 2 h after treatment and in the placenta at 4 h. At 12 It significantly lower concentrations of several amino acid including methionine were found in the placentae and fetuses in the treated group. After 24 h, no difference was seen in the plasma amino acid concentrations but in the placentae and fetuses a significant decrease occurred in some amino acids in the treated group. At 48 and 72h, a generalized increase in most amino acid levels occurred in the fetus and placenta but not in maternal plasma of the treated group although the fetal and placental weights were significantly reduced. VGB during late gestation causes fetal growth retardation accompanied by an initial disruption of amino acid supply followed by an increase in amino acid concentrations for the next 2 days. This increase did not help restore growth suggesting that early fetal period is particularly vulnerable to VGB-induced intrauterine growth retardation in the mouse. (c) 2005 Elsevier Inc. All rights reserved.