Effects of Acute Ethanol Exposure upon In Vivo Leucine Uptake and Protein Synthesis in the Fetal Rat

Abstract

Summary: Tritiated L-leucine (l³HlL-leu) was injected into the amniotic saes of 19-day gestation rat fetuses during a brief (4-hr) period of elevation in maternal serum ethanol. The pregnant rats received 47.5% ethanol at “high dose” (0.29 to 0.33g/100g body weight) or “low dose” (0.12 to 0.14 g/100gm body weight) by intraperitoneal injection. Fetal brain and liver were removed and analyzed for tissue uptake (TU) and protein incorporation (PI) of [³H]l-leu. Relative protein synthesis, independent of alterations in TU, was expressed by the ratio Pl/TU × 100. Delayed fetal effects of acute maternal ethanol exposure were studied by injecting the fetal amniotic sacs with [³H]l-leu 24 hr after maternal ethanol administration. Both TU and PI were decreased in bigh dose fetal brain. Liver PI, but not TU, was depressed. High dose ethanol treatment caused a reduction in protein synthesis (PI/TU × 100) in fetal brain, but not liver. Low dose ethanol enhanced brain PI and both liver and brain PI/TU × 100. Utilization of [³H]L-leu was related to fourth-hour (sacrifice) maternal serum ethanol levels. Fetal brain was more strikingly affected than liver. Ethanol concentrations >200 mg/dl caused a decrease in brain TU (control, 1879 ± 185 versus ethanol, 1219 ± 123 dpm/mg protein) and PI/TU × 100 (control, 48.9 ± 3.3 versus ethanol, 31.5 ± 2.9). At levels versus ethanol, 31.5 ± 2.9). At levels versus ethanol, 67.3 ± 2.8) and liver (control, 45.3 ± 4.2 versus ethanol, 62.3 ± 1.7). Tissue uptake of [³H]L.-leu 24 hr after high dose maternal ethanol exposure was increased in fetal brain. The results support the hypothesis that a brief period of maternal/fetal ethanol exposure, similar to that found in “social” drinking humans, alters normal fetal metabolism. Speculation: Chronic maternal ethanol abuse is harmful to the human fetus, but the fetal risks of acute or “social” ethanol consumption are undefined. The observation of altered rat fetal utilization of leucine both during and 24 hr after acute maternal ethanol administration suggests that even a brief period of ethanol exposure is potentially harmful to the fetus. The long-term effects of such exposure upon fetal and neonatal growth and development remain to be determined.