UC Riverside

Alcohol exposure during fetal development is the leading known preventable cause of mental retardation in the western world (Abel et al., 1995; Abel et al., 1987; Stratton et al., 1996). Animal models and human studies reveal deficits in sensory-processing, behavior, motor learning, spatial functioning, and increased anxiety as a result of prenatal ethanol exposure (PrEE; Glavas et al., 2001; Kalberg et al., 2006; Hellemans et al., 2010; Carr et al., 2010; Hamilton et al., 2010). Work in the Huffman Laboratory has demonstrated how PrEE can induce abnormal neocortical gene expression, mistargeting of intraneocortical connections, changes to brain anatomy, and altered behavior in the first filial (F1, directly exposed) generation (El Shawa et al., 2013), as well as ethanol’s ability to induce epigenetic modifications (Abbott et al., 2017). If PrEE-induced epigenetic modifications contribute to the observed abnormal gene expression in PrEE animals, then it is plausible that PrEE related conditions could be heritable across generations without further exposure. By extending the metrics used to assess the first generation, we discovered stable modifications to brain anatomy, connectivity and behavior that is detectable across three generations. Many of the anatomical and connectivity related phenotypes are detectable at birth, and behavior is altered across all three generations when measured in prepubescent mice. Cataloging the effects that persist across multiple generations provides strong evidence for ethanol-induced epigenetic changes during development and provides insights into some of the mechanisms influencing heritability. The final study of this dissertation assesses the general perception of safe dietary behavior during pregnancy including alcohol. Responses demonstrated a lack of understanding about the danger of items containing teratogens like BPA, mercury and prescription pain medications and revealed a misconception about the safety of periodic wine drinking throughout pregnancy. The safety of alcohol as scored on our survey approximated CDC statistics of actual consumption during pregnancy. It is clear that increased education about the dangers of teratogen consumption, such as alcohol, during pregnancy is critical for the health and well being of future generations