Effects of ethanol on glucose utilization by cultured mammalian embryos

We have previously observed correlations between placental glucose transfer and growth of fetuses of ethanol (EtOH)-fed and control rats. In the present study, whole mammalian embryos were used to define the interaction of glucose supply and the effects of EtOH on growth and differentiation. Rat embryos were cultured in 75% normal rat serum from day 9.5 to day 11.5 of gestation. EtOH produced dose-dependent reductions of embryo protein content (mean +/- SEM = 212 +/- 5, 171 +/- 11, 141 +/- 16, and 113 +/- 9 micrograms/embryo in the presence of 0, 25, 50, and 100 mM EtoH, respectively). Somite number was 25.7 +/- 0.3, 23.4 +/- 0.7, 21.8 +/- 0.7, and 21.1 +/- 0.4 under the same conditions. Exposure to ethanol during the first 24 hr in culture decreased embryo protein content to the same extent as exposure for the entire 48-hr culture period. After 46 hr in culture, control and ethanol-exposed embryos were incubated with 14C-glucose for 2 hr. Ethanol produced dose-dependent reductions of CO2 production, anabolic utilization, lactate release, and total glucose utilization. Glucose supplementation (300 mg/dl) significantly increased embryo protein content and each of these glucose utilization parameters. When glucose utilization was expressed relative to embryo protein content, incorporation of the label into embryonic tissues was significantly reduced by ethanol and increased by glucose supplementation. Embryo protein content correlated closely (r = 0.871, p less than 0.0001) with anabolic glucose utilization. Thus, ethanol directly affects embryo glucose utilization, both as an energy source and as a synthetic substrate, in addition to its effects on placental glucose transfer.