DNA methylation is the most commonly studied epigenetic modification as related to developmental alcohol exposure. PAE is associated with alterations in methylation and hydroxymethylation patterns in the developing brain (Chen et al., 2013; Dasmahapatra and Khan, 2016) (Figure 1). Alcohol exposure during mid-to-late gestation disrupted the normal DNA methylation program in the fetal hippocampus through dysregulation of proteins governing methylation and hydroxymethylation, including methyltransferases (Garro et al., 1991), TET1, and methyl-CpG-binding protein (MeCP2) (Chen et al., 2013; Subbanna et al., 2014). The hippocampus of alcohol-exposed fetuses also showed evidence of developmental delay, with fewer cells in the dentate gyrus displaying markers related to mature neuronal status (Chen et al., 2013). However, there was a reduction in the progenitor pool (Ki-67+) as well, indicating the loss of mature neurons could be due to apoptosis or to slower cell cycle progression. Increased time to progress through the cell cycle in combination with apoptosis has been documented in multiple models of FASD and is a contributing factor to the developmental delay in embryonic maturation (Luo and Miller, 1998; Luo et al., 1999; Zhou et al., 2011).
