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Chunk #81 — Future Directions: Combining Stress and Alcohol Models and Assessment of Multigenerational Effects and Therapeutics — Multigenerational Effects

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Epigenetic mechanisms in alcohol- and adversity-induced developmental origins of neurobehavioral functioning.
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directly assessed in the offspring, numerous reports of behavioral and physical abnormalities have been reported following paternal alcohol exposure (Abel and Lee, 1988; Bielawski and Abel, 1997; Ledig et al., 1998); epigenetic changes carried through the germline are one way to envision how paternal drinking could affect offspring. Knezovich and Ramsay (2012) reported significant reductions in CTCF, a transcription factor sensitive to methylation at its target DNA binding sites and that regulates methylation patterns and chromatin structure related to clustered protocadherins and paternally methylated imprinting control regions of DNA, including H19 and RASgrf1. However, analysis of sperm methylation in males revealed no differences following alcohol exposure, indicating that the methylation changes in the offspring must be due to some other epigenetic mechanism. Further confirming the sensitivity of the male germline to alcohol, transgenerational changes to Pomc methylation status and mRNA levels were reported through the F3 male germline following PAE, while the female germline was not affected (Govorko et al., 2012).