Given the above considerations, the potential influence of maternal cigarette smoking during pregnancy on epigenetic mechanisms which may have consequences for downstream behavior is manifold. First, there is the possibility of intergenerational transmission of smoking-related epigenetic consequences (i.e., grandmaternal smoking influences may affect germline cells or may escape epigenetic reprogramming during development). Second, we can begin to understand the extent to which epigenetic modification may alter critical neurobehavioral circuitry in the developing brain. Third, questions regarding the influence of smoke exposure-induced methylation on the xenobiotic metabolism of cigarette smoke by-products can begin to be answered. These are just a few of the currently unanswered questions for which epigenetic research might begin to provide answers. Fortunately, at least for DNA methylation, existing datasets with collected DNA samples may provide some opportunities to investigate such possibilities. For example, methylomic characterization of samples collected in sibling pairs discordant for prenatal exposure might provide initial evidence of longer lasting impacts of pre-pregnancy smoking that may make maternal smoking during pregnancy per se less important than overall maternal smoking history. Use of animal models in
