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Chunk #16 — Prenatal Alcohol Exposure — DNA methylation

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Epigenetic mechanisms in alcohol- and adversity-induced developmental origins of neurobehavioral functioning.
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Growth restriction is commonly found in offspring exposed to alcohol during gestation. Insulin-like growth factor 2 (IGF-2), along with other growth-promoting hormones, is important for appropriate age-associated growth during gestation. PAE alters methylation patterns of Igf2 in the placenta of alcohol-treated dams (Haycock and Ramsay, 2009), embryonic tissue (Downing et al., 2011), and adult brain tissue (Laufer et al., 2013). Downing and colleagues (2011) also demonstrated that Igf2 expression was downregulated following PAE; gene expression was not directly measured in the other two studies. IGF-2 plays a critical role in embryonic development, as knockdown of Igf2 results in severe growth retardation and bone growth delay (Baker et al., 1993). Alcohol-treated embryos were observed to be significantly smaller in the study by Haycock and Ramsay (2009), while weight differences were not reported in the other two studies. Brain-derived neurotrophic factor (BDNF) is another growth factor important for cell proliferation, dendritic outgrowth, and synapse formation, particularly in the adult brain. Numerous studies have demonstrated that development alcohol exposure causes long-term changes to functional and anatomical measures linked to BDNF signaling, including long-term