Over the past nine years, maternal alcohol consumption has become recognized through extensive human and animal studies as a major fetal health hazard--a leading known cause of mental retardation. Understanding the mechanism(s) by which alcohol exerts its effects is most essential in therapeutic intervention. The proposed study will test the hypothesis that fetal malnutrition in amino acid(s) and/or certain vitamins (thiamin, vitamin B6 and folic acid), is the cause of the fetal alcohol syndrome (FAS) and that this fetal nutritional deficiency is the consequence of maternal alcohol consumption leading to impaired placental function in nutrient transfer and maternal nutrient absorption and metabolism. Groups of female rats will be maintained on chemically defined liquid diets containing 30% or 20% ethanol derived calories during gestation (gestation-day 7 to 21) or prior to and throughout gestation (at least 21-days pregestation to gestation-day 21). Pair-fed controls and stock diet-fed controls will be employed for comparison. On gestation-day 21, pregnant rats will be sacrificed for the determination of vitamins and free amino acids in maternal, placental and fetal tissues to assess the nutritional status of fetuses, their mothers and placental function. Fetuses will also be examined for external and internal anomalies to determine if any correlation exists between their nutritional status and the extent of malformation. The effect of diets marginal in vitamins or protein, common among alcoholics, as a risk factor in developing fetal nutritional deficiency and physical anomalies will also be investigated. Since it was found in preliminary studies that fetal plasma free histidine levels were greatly influenced by maternal alcohol consumption, the effect of maternal alcohol ingestion on the metabolism of histidine will also be investigated by examining (1) the urinary production of histamine; (2) the fetal, placental and maternal tissue levels of histidine, histamine, histamine synthesizing and metabolizing enzymes (histidine decarboxylase and histamine methyltransferase); and (3) levels of the histidine containing dipeptides, carnosine and anserine, in alcohol-fed and control rats, and also in rats fed three levels of dietary histidine, with or without alcohol.
| Lin, G W (1991) Maternal-fetal folate transfer: effect of ethanol and dietary folate deficiency. Alcohol 8:169-72 |
| Lin, G W; Lin, T Y; Jin, L (1990) Gestational ethanol consumption on tissue amino acid levels: decreased free histidine and tryptophan in fetal tissues with concomitant increase in urinary histamine excretion. Alcohol Clin Exp Res 14:430-7 |
| Lin, G W (1989) Liquid diet preparation for study of chronic alcohol ingestion in the rat. Lab Anim Sci 39:618-20 |
| Lin, G W (1989) Effect of ethanol and vitamin B6 deficiency on pyridoxal 5-phosphate levels and fetal growth in rat. Alcohol Clin Exp Res 13:236-9 |
