The intensity and duration of the prenatal stressor is another factor that mediates the long-term impacts of prenatal stress, as opposite effects have been observed in the epigenome and behavior of animals incurring mild versus high prenatal stress. For example, both male and female offspring experiencing mild prenatal stress exhibited increased global methylation, while offspring exposed to high stress showed reduced global methylation in the hippocampus at PD21 (Mychasiuk et al., 2011). Mild stress reduced locomotor activity, while high stress increased locomotor activity. Timing of the gestational stressor is also critical in determining the effects the stressor will have on offspring, as neural systems develop at different gestational time points leaving different system vulnerable at different times of gestation. Multiple studies have demonstrated time-specific effects of prenatal exposure to stress (Heijmans et al., 2008; Mueller and Bale, 2008; Tobi et al., 2009).
