Inhibition of Placental Amino Acid Uptake in Rats Following Acute and Chronic Ethanol Exposure

Abstract

The effects of acute and chronic maternal ethanol consumption on in vitro placental uptake of alpha-aminoisobutyric acid (AIB), cycloleucine, L-alanine (Ala), L-leucine (Leu), and L-lysine (Lys) were determined. Ethanol (4 g/kg. po) administered 2 hr prior to sacrifice, reduced (p less than 0.05) placental villous net uptake of cycloleucine and Ala by 29%. Prior chronic ethanol consumption depressed (p less than 0.05) placental uptake of AIB (38%), cycloleucine (45%), Ala (35%), Leu (25%), and Lys (34%). In vitro exposure of previously untreated villous fragments for 2 hr to 2 mg/ml of ethanol reduced (p less than 0.05) the net uptake of AIB and cycloleucine by 24% and 31%, respectively, whereas the minimum concentration of acetaldehyde required to cause a significant inhibition was 310 microM for AIB and 465 microM for cycloleucine. Ethanol (3 mg/ml) had no effect on AIB or cycloleucine net uptake if sodium was omitted from the incubation media. The efflux of AIB (10(-6)M) and cycloleucine (10(-6)M) from villous tissue was unaffected (p less than 0.05) by either ethanol (3 mg/ml) or acetaldehyde (600 microM) and obeyed first order kinetics. It was concluded that acute, and especially chronic, maternal ethanol consumption can depress the placental uptake of a variety of amino acids in the rat and, in the acute setting, the effect was on a sodium-dependent system involved in amino acid influx into placental cells.

Prenatal Alcohol Exposure: Abnormalities in Placental Growth and Fetal Amino Acid Uptake in the Rat

“…Both normal placental and decreased fetal amino acid accumulation seen in the current study could be due to either abnor mal amino acid transport out of the placenta, a process shown to require active transport [26], or to a primary defect in the fetus. Nor mal amino acid efflux from the rat placenta has been reported after in vitro incubation with ethanol [4] thus, supporting the hypoth esis for a primary defect in fetal uptake.…”

“…Rats fed alcohol in daily amounts equivalent to 30-36% of the total caloric intake have reduced rates of in vivo placental transfer of valine, zinc and alpha-amino-isobutyric acid [1][2][3]. In vitro studies have also shown reduced placental transport capacity for various amino acids in alcohol-fed rats [4].…”

Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep

“…Nutrient supply to the fetus may nevertheless be profoundly compromised and contribute to fetal growth retardation in this model due to the effects of ethanol on placental function. Ethanol impairs placental uptake and/or delivery to the fetus of glucose and amino acids in rats and humans (20,21,40,41). Ethanol may also impair fetal tissue uptake of nutrients from the fetal circulation, for example by decreasing the expression and activity of glucose transporters.…”

Effects of Maternal Ethanol Ingestion on the Uptake of Alpha-Aminoisobutyric Acid by Fetal Rat Liver, Lung and Brain

“…Lin [1] reported a signifi cant reduction of the transfer of the alanine analog a-aminoisobutyric acid (AIB) to the placenta and fetuses of rats fed 30% ethanol-1 derived calories during the last 2 weeks of gestation. Henderson et al [2,4] and Patwardhan et al [3] reported reduced placental uptake and transfer of various amino acids after chronic and acute ethanol consumption by pregnant rats. In addition, Fisher et al [5,6] demonstrated reduced AIB uptake in vitro by placental slices from non-human pri mates fed ethanol during pregnancy and by human placental slices incubated with high doses of ethanol [7],…”