The role of maternal diet in the developmental toxicology of ethanol

A commonly observed result of ethanol administration to experimental animals is a reduction in voluntary dietary intake. The purpose of this investigation was to examine the role of this reduction in the developmental/reproductive toxicity of ethanol. To achieve this objective, female C3H mice were administered one of the following diets from Day 0 to Day 17 of pregnancy: (1) liquid diet, (2) liquid diet plus 4.1% w/v ethanol, (3) an amount of liquid diet equal to that consumed by the liquid diet plus 4.1% w/v ethanol group, i.e., pair-fed, (4) liquid diet fortified with protein, fats, carbohydrates, vitamins, and minerals, or (5) fortified diet plus 4.1% w/v ethanol. An important aspect of this experiment was the 2 X 2 factorial design, which permitted the analysis of the effects of ethanol consumption, diet intake reduction, and potential interactions between these two factors. After maternal death on Day 17 of gestation, fetuses were examined for evidence of alterations in growth and/or development. Analysis of the results revealed that decreased dietary intake, but not ethanol consumption resulted in a decrease in fertility, maternal pregnancy weight gain, and litter size. In contrast, both decreased dietary intake and ethanol consumption significantly inhibited fetal growth and development. However, no interaction between these two factors was demonstrated, indicating that ethanol's fetotoxic effects occurred, regardless of maternal dietary intake. We conclude that, depending on the endpoint examined, maternal nutrition plays a key role in experimental ethanol fetotoxicity. However, this agent is fetotoxic, even in the well-nourished animal.