Rodents exposed to alcohol in utero often display increased depressive- and anxiety-like behaviors later in life (Brocardo et al., 2012; Caldwell et al., 2008; Hellemans et al., 2010; Hellemans et al., 2008). Children with FASD also present with psychopathology at a greater rate than their peers (O'connor and Paley, 2009; Steinhausen and Spohr, 1998). PAE might impact stress reactivity by altering long-term HPA axis functioning through epigenetic regulation. Hypermethylation of the proopiomelanocortin (POMC) gene (Bekdash et al., 2013), a polypeptide that serves as a precursor for pituitary-produced hormones including adrenocorticotropic hormone, β-endorphin, and met-enkephalin, was reported in the adult rat hypothalamus. Concomitant reductions in Pomc mRNA levels were also observed. Increases in one-carbon metabolism, involved in the production of methyl donors, were also reported in the hypothalamus following PAE (Ngai et al., 2015). Developmentally alcohol exposed rats exhibited a short-term increase in plasma corticosterone levels and overactive corticosterone responses to lipopolysaccharide (LPS) in adulthood, further linking developmental alcohol exposure to alterations in stress responsivity (Bekdash et al., 2013; Boschen et al., 2015; Kim et al., 1999).
