Despite the considerable work done characterizing epigenetic modifications in models of developmental alcohol or stress, many questions remain. First, compared to the depth of knowledge stemming from the developmental stress literature, FASD researchers are still in the beginning stages of their investigations regarding how in utero alcohol alters epigenetic patterns and if changes to the epigenome causally relate to behavioral outcomes and can be used as reliable biomarkers. Many studies that assess epigenetic endpoints do not include analysis of downstream gene or protein expression. These additional measures can help determine the functional consequences of the epigenetic marks. Furthermore, it is unknown if alterations to epigenetic status in a cell population are always due to de novo changes following an exposure to stress or alcohol or if these changes are representative of preexisting marks that distinguish certain cell populations. As PAE and stress can induce apoptosis (Farber et al., 2010; Heaton et al., 2003; Kim et al., 2015), it is possible that the surviving cell population has a certain epigenetic profile that becomes apparent following the widespread cell death. While this alternative is unlikely to always be the case, it is a hypothesis that should be explored.
