Alcohol consumption during pregnancy can impact genome regulation in developing offspring, but research findings have been inconsistent. Our study utilized a murine model of short-term, moderate prenatal alcohol exposure (PAE) that mimics typical patterns of alcohol use in human pregnancies. We found that even early moderate PAE was enough to cause site-specific DNA methylation changes in newborn pups, though it didn't alter behavioral outcomes in adult mice.
Using whole-genome bisulfite sequencing on neonatal brain and liver tissue, we observed a stochastic and mostly tissue-specific effect on DNA methylation. Some of these effects might even originate as early as gastrulation. Replication studies in human cohorts with Fetal Alcohol Spectrum Disorder (FASD) suggested that some of these effects were metastable in genes associated with disease-relevant traits, including intelligence, facial morphology, educational attainment, autism, and schizophrenia.A key finding from our murine model was that a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation.
These results show that early moderate alcohol exposure can affect fetal genome regulation even without visible phenotypic changes and highlight the potential of maternal dietary interventions as a preventative strategy. While our findings require cautious interpretation due to the study's small sample size and potential confounders, they support the idea that alcohol-induced epigenetic disruption may be partly due to interference with one-carbon metabolism.