Maternal alcohol consumption has been recognized through extensive human and animal studies as a major fetal 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 ethanol-induced alterations in fetal nutritional state is one of the causes of fetal alcohol syndrome (FAS) and that maternal nutritional deficiency potentiates ethanol teratogenicity. The nutrients to be examined in this proposal are folic acid and histidine. Groups of rats will be fed chemically defined liquid diets containing 35% ethanol calorie or isocaloric sucrose with 500 ug/l or 50 ul/l of folic acid. Pregnancy outcome will be examined on gestation-day 21. Tissues will be analyzed for total folates, individual folate monoglutamates, folate polyglutamates and 5-methyltetrahydro folate homocysteine methyltransferase to assess the extent of ethanol effect on folate metabolism under different folate nutritional states. Effect of ethanol on maternal-fetal transfer of folic acid will also be investigated in rats maintained on either folate sufficient or deficient diets. In chronic study, rats will be fed liquid diets (35% ethanol-calorie or isocaloric sucrose). In acute study ethanol will be given I.G. prior to transport performance. Labeled folic acid, given I.V., will be used to assess the transport function by determining the distribution of radioactivity in maternal, fetal and placental tissues. Effect of chronic ethanol consumption on histidine metabolism in relation to histimine formation and fetal development will be evaluated by feeding pregnant rats ethanol diet containing various levels of histidine (0.1, 0.3 and 0.8% cal) and examining urinary histamine excretion, pregnancy outcome and tissue contents of histidine, histamine and histamine synthesizing and degradating enzymes.
| 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 |
