Distinct Effects of Maternal Stress and Exercise on Offspring Metabolic Health

Maternal physical activity enhances offspring metabolic resilience, whereas prenatal psychosocial stress predisposes offspring to lifelong metabolic dysfunction. Whether maternal exercise can attenuate the deleterious programming effects of stress has remained unclear. Here, we investigated the effect of maternal exercise and/or prenatal psychosocial stress on the metabolic health of male and female offspring. C57BL/6 dams were assigned to four conditions: sedentary/non-stressed (SED-NS), sedentary/stressed (SED-S), exercised/non-stressed (EX-NS), or exercised/stressed (EX-S). Male EX-NS offspring had improved glucose tolerance compared to SED-NS and SED-S; however these effects were blunted in male EX-S offspring, indicating that prenatal stress abolished this exercise-induced benefit. In contrast, there was no effect of maternal stress or exercise on glucose tolerance in female offspring. Maternal exercise chronically elevated basal corticosterone in male offspring, regardless of maternal stress. Maternal stress increased mineralocorticoid receptor (Nr3c2) mRNA and glucocorticoid receptor (NR3C1) protein expression in brown adipose tissue in male mice, while exercise restored NR3C1 expression. These findings indicate that prenatal stress blunts the metabolic benefits of maternal exercise in male offspring and is associated with altered corticosteroid signaling in brown adipose tissue. Together, the data identify a stress-exercise interaction that may influence offspring metabolic programming through tissue-specific regulation of glucocorticoid pathways.