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Chunk #80 — 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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One of the most important and fascinating implications of epigenetic modifications is the potential for intergenerational or transgenerational transmission. Intergenerational transmission involves direct exposure of a teratogen on the germline, whereas transgenerational transmission excludes direct exposure (for example F2 generation involving the paternal germline or F3 involving the maternal germline) (Klengel et al., 2016). Both PAE and developmental stress have been shown to have multigenerational effects through epigenetic modifications to the germline (Figure 3). While the literature regarding inter- and transgenerational epigenetic effects associated with PAE is limited, there is evidence that paternal experience with alcohol has an impact on methylation patterns in the germline. For example, males rats exposed to alcohol for 9 weeks had significant changes to methyltransferase levels in their sperm and produced offspring with lower birth weight (Bielawski et al., 2002). While methylation patterns were not 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