Maternal exercise is associated with enhanced systolic reserve and altered mitochondrial respiration in adult female offspring

Maternal exercise may influence long-term cardiovascular health in offspring, yet its effects on intrinsic myocardial performance and mitochondrial metabolism remain incompletely defined. We investigated whether maternal voluntary wheel running before and during pregnancy is associated with cardiac adaptations in adult offspring. Female C57BL/6J mice were assigned to sedentary (Sed) or exercise (Ex) groups, with running initiated 3 weeks before mating and continued through gestation and lactation. Adult offspring (29–32 weeks) underwent high-fidelity pressure-volume (P-V) loop analysis at baseline and, in females, during β-adrenergic stimulation to assess systolic reserve. Cardiac mitochondria were evaluated by high-resolution respirometry together with measurements of reactive oxygen species emission. Maternal exercise did not alter maternal body weight before delivery or adult offspring body weight, whereas cardiac mass index was significantly lower in A-Ex offspring than in A-Sed offspring. Baseline hemodynamics were largely similar between maternal groups. In females, maternal exercise was associated with lower end-systolic elastance (E es ) at rest and a greater dobutamine-induced increase in E es , consistent with enhanced load-independent systolic reserve. Mitochondrial analyses revealed substrate-dependent adaptations in females: maternal exercise was associated with lower pyruvate/malate-supported LEAK respiration, higher fatty acid-supported LEAK respiration, and reduced fatty acid coupling efficiency compared with sedentary offspring. ROS emission, sarcoplasmic reticulum Ca 2+ -handling proteins, fetal gene expression, and collagen-related transcript expression were unaffected. These findings suggest persistent functional and mitochondrial respiratory adaptations in adult offspring following maternal exercise, with the clearest adaptations observed in females.