Impact of prenatal stress on long term body weight is dependent on timing and maternal sensitivity

Stress experienced during pregnancy increases the risk for altered birth weights. Recent studies have revealed a link between abnormal birth weights and a future predisposition toward developing overweight or obesity. To determine the gestational time window when stress exposure produces the greatest impact on offspring body weight regulation, we have examined the birth weights and long-term body weight changes in offspring exposed to chronic variable stress (CVS) early, mid-, or late in gestation. As it is likely that the influences of prenatal stress on development stem from a complex interaction between both environmental and genetic factors, our study has included comparisons with offspring born to stress-sensitive (corticotropin-releasing factor receptor-2 deficient) mice. Stress experienced late in pregnancy significantly elevated offspring birth weights in wild type mice compared to unstressed controls. However, this weight difference diminished postnatally. In contrast, stress experienced mid- to late in pregnancy produced significant and long-term effects on body weight in offspring from stress-sensitive dams, were the male offspring were 15% heavier as adults. Adult offspring plasma glucose and leptin levels were also dependent on the timing of stress exposure, indicating that alterations in energy homeostasis may be influencing long-term body weight. Results from these studies support our hypothesis that the ultimate effect of prenatal stress on offspring long-term outcome is dependent on the timing of exposure and maternal sensitivity.