Although maternal alcoholism is recognized as a major risk to the fetus, the pathogenesis of its effects remains unclear. We have previously observed reduced blood glucose and insulin levels in term fetuses from ethanol-fed rats. Moderate ethanol intake decreased the placental transfer of glucose, and fetal body weights correlated with placental glucose transfer. Aberrations in fetal fuel mixtures have been shown to retard growth and produce dysmorphogenesis. Thus, alterations in glucose supply and metabolism may play a role in the effects of exposure to ethanol in utero. However, the feeding of ethanol in liquid diet during gestation presents problems in the control of nutritional status. In addition, those factors most of interest, fetal glucose and insulin levels, cannot be easily or independently controlled in vivo. The proposed studies would address this question in two in vitro systems. Whole embryo culture has been shown to be suitable for metabolic and teratogenic studies. The effects of ethanol (25-100 mM) and acetaldehyde (25-100 uM) on embryo growth will be assessed by increase in length, somite number, protein and DNA content, and by the rates of incorporation of radiolabeled substrates into protein, RNA, and DNA. Relationships will be examined between effects on growth and effects on fuel (glucose and ketone) transport and utilization (glucose uptake from medium, lactate production, incorporation into tissue constituents, and CO2 production). Effects on the binding of insulin and insulin-like growth factors by the embryo and extraembryonic membranes will be determined. Parallel studies will be conducted using fetal hepatocyte cultures initiated on the nineteenth day of gestation. In addition, glucose, ketone, and insulin levels will be varied in the medium of both culture systems to determine whether specific alterations can exacerbate or counteract the effects of ethanol or acetaldehyde on the growth and differentiation of the embryo.
