Ethanol teratogenesis in mice selected for differences in alcohol sensitivity.

Area of Science:

• Toxicology
• Genetics
• Developmental Biology

Background:

• Ethanol (alcohol) exposure during pregnancy can cause fetal alcohol spectrum disorders.
• Genetic factors may influence an individual's susceptibility to the teratogenic effects of ethanol.

Purpose of the Study:

• To investigate the impact of genetic differences in alcohol sensitivity on the fetotoxic effects of prenatal ethanol exposure.
• To compare the effects of ethanol on fetal development in Long-Sleep (LS) and Short-Sleep (SS) mice, which exhibit differential sensitivity to ethanol-induced narcosis.

Main Methods:

• Long-Sleep (LS) and Short-Sleep (SS) mice were administered varying doses of ethanol (2.9-10 g/kg/day) twice daily during organogenesis.
• On gestation day 18, dams were sacrificed, and fetuses were examined for viability, body weight, skeletal anomalies, and soft tissue anomalies.

Main Results:

• Ethanol doses up to 5.0 g/kg/day did not affect prenatal mortality, litter size, or physical anomalies in either mouse line.
• Higher ethanol doses (≥8.0 g/kg/day) led to decreased fetal body weight in alcohol-sensitive LS mice, with effects seen only at the highest dose in alcohol-insensitive SS mice.
• The incidence of skeletal variants increased in LS mice exposed to 10 g/kg/day ethanol.

Conclusions:

• Genetically mediated differences in alcohol sensitivity affect susceptibility to prenatal ethanol toxicity.
• LS mice, being more sensitive to alcohol, exhibited greater adverse effects on fetal development compared to SS mice.
• These findings highlight the role of genetic background in moderating the teratogenic potential of in utero ethanol exposure.