Early prenatal but not postnatal glucocorticoid exposure is associated with enhanced HPA axis activity into adulthood in a wild primate

The hypothalamic-pituitary-adrenal (HPA) axis plays a dual role in the biology of developmental plasticity in mammals including humans — as a generalized response to experienced adversity, HPA activity not only provides the input for, but is also the target of offspring developmental plasticity. To investigate the understudied effects of exposure timing, this study quantified maternal HPA axis activity during each gestation semester and during early lactation and assessed its effect on offspring HPA axis activity in a cross-sectional sample of infant, juvenile, and adult Assamese macaques (Macaca assamensis). To add ecological validity to experimental studies under lab conditions, macaques were studied in the wild where within- and between-year variation in food scarcity acts as one adversity causing moderate variation in maternal HPA axis activity between mothers and between different reproductive phases. Increased maternal fecal glucocorticoid metabolite levels experienced early in gestation, but not exposure during lactation were associated with increased offspring HPA axis activity suggesting a timing effect. The same response to early prenatal exposure, i.e. increased average, maximum and range of offspring fecal glucocorticoid levels, was observed from infancy into adulthood. Building on prior findings, this study indicates that significant timing effects not only influence the presence, magnitude, and direction, but also the consistency of maternal glucocorticoid effects on offspring HPA axis function. The first semester of gestation is a period of development that many animal and human studies do not independently investigate, but where the central axis of the stress response seems particularly sensitive to programming effects.