Search

Since the first reports of fetal alcohol syndrome (FAS), thousands of studies have examined the effects of antenatal alcohol exposure in humans and in animal models. Research with animal models has led to discoveries which would be difficult if not impossible in human subjects. Most importantly, these models have resulted in valuable insights into the actions of alcohol on various parts of the developing embryo and have helped researchers come closer to identifying the mechanisms of its teratogenic action. Both the direct and indirect biological effects of alcohol exposure in utero appear to work in conjunction with other concurrent and predisposing factors such as genotype, nutritional status, pattern of exposure and use of other drugs such as nicotine and cocaine. At present animal research indicates a multifactorial mechanism of the teratogenicity of alcohol resulting from nutrient deficiencies, fetal hypoxia and alterations in enzyme activities and cell function important in cell division and membrane integrity. This review examines how animal models are used to clarify issues associated with alcohol-related birth defects and to shed light on the underlying mechanisms.

Two studies were conducted to evaluate the interactive effects of alcohol and lead during pregnancy in rats. Our purpose was to see if lead, as lead acetate, would influence the alcohol effect already known to exist. In the first study, pregnant Long-Evans rats received lead (as lead acetate), alcohol (20% w/v), or lead plus alcohol once a day on gestation days (GD) 10-20. On GD 20, when animals were sacrificed, mean blood alcohol levels were consistently higher for the lead-plus-alcohol-dosed groups compared to alcohol alone, but these two groups did not differ in maternal weight gain, percent resorptions, litter size, or fetal weight. Mean blood lead levels were not consistently higher in the lead-plus-alcohol groups compared to lead only, but the lead-plus-alcohol groups differed significantly from the lead-only groups at higher doses in the previously mentioned parameters. The lead-only groups did not differ from vehicle controls in any parameter in spite of blood lead levels as high as 300 micrograms/dl. In the second experiment, animals given a combination of alcohol and lead did not differ in activity, passive avoidance, or active avoidance learning compared to animals given alcohol or lead alone. Animals given lead only or the combination of lead plus alcohol had longer first trial latencies in the passive avoidance test. The data indicate that neither lead nor alcohol attenuates or potentiates each other's effects on reproduction or learning behavior in the Long-Evans rat even at high blood lead levels.

Pregnant Swiss Webster mice were given a liquid diet with ethanol (EtOH) or isocaloric amounts of maltose dextrin on gestation day (GD) 0 through 18. On GD 18, maternal blood samples were obtained. Fetuses were then removed and fetal brains were prepared for light microscopy. Fetal weight was reduced in the EtOH-exposed group. The ratio of midbrain cross sectional area to cerebral aqueduct was reduced in the ethanol group, while the density of neuronal nuclear population in both the dense outer layer (DS) and sparse inner layer (SS) of the developing superior colliculus was increased. Mean nuclear volume was decreased in the SS.

The red nucleus of Swiss Webster mouse fetuses was examined for morphological changes following maternal ethanol exposure. Pregnant females were given a liquid diet containing 30% or 0% ethanol-derived calories. Changes in numerical density of neurons and in neuronal nuclear volume were found in the rostral red (RR) nucleus of ethanol-exposed pups but not in the caudal red (CR) nucleus. Because of the integrative nature of the RR, changes in neuronal morphology that might relate to synaptic connections could affect the behavioral response mechanisms of these off spring.