Effects of acute ethanol exposure upon in vivo leucine uptake and protein synthesis in the fetal rat.

Abstract

Tritiated L-leucine ((3H)L-leu) was injected into the amniotic sacs 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 0.33 g/100 g body weight) or "low dose" (0.12 to 0.14 g/100 gm 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 PI/TU x 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 high dose fetal brain. Liver PI, but not TU, was depressed. High dose ethanol treatment caused a reduction in protein synthesis (PI/TU x 100) in fetal brain but not liver. Low dose ethanol enhanced brain PI and both liver and brain PI/TU x 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 greater than 200 mg/dl caused a decrease in brain TU (control, 1879 +/- 185 versus ethanol, 1219 +/- 123 dpm/mg protein) and PI/TU x 100 (control, 48.9 +/- 3.3 versus ethanol, 31.5 +/- 2.9). At levels less than 100 mg/dl, PI/TU x 100 was enhanced in both brain (control, 48.9 +/- 3.3 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.