to clearly define the nature of gene-environment interactions during development and how such effects result in the sustained “environmental programming” of gene expression and function over the life span. Finally, it is important to note that maternal effects on the expression of defensive responses, such as increased HPA activity, are a common theme in biology,132,133 such that the magnitude of the maternal influence on the development of HPA and behavioral responses to stress in the rat should not be surprising. Maternal effects on defensive responses to threat are apparent in plants, insects, and reptiles. Such effects commonly follow from the exposure of the mother to the same or similar forms of threat and may represent examples where the environmental experience of the mother is translated through an epigenetic mechanism of inheritance into phenotypic variation in the offspring. Indeed, maternal effects could result in the transmission of adaptive responses across generations.30 Epigenomic modifications of targeted regulatory sequences in response to even reasonably subtle variations in environmental conditions might serve as a major source of epigenetic variation in gene expression and function, and ultimately as a process mediating such maternal effects. We propose that epigenomic changes serve as an intermediate process that
