Abstract

Background and Objective: Evidence suggests that maternal physical activity can influence the cardiovascular health of the next generation through developmental programming. Although the beneficial effects of maternal exercise on several cardiac and metabolic outcomes in offspring have been reported, the effects of the timing of maternal high-intensity interval training (HIIT) on cardiac angiogenic factors and sex-related differences have not been directly investigated. Therefore, the present study aimed to investigate the interactive effects of offspring sex and the timing of maternal physical activity on cardiac angiogenic factors in Wistar rat offspring.

Materials and Methods: In this experimental study, 32 female Wistar rats (8 rats per group) were randomly assigned to four groups: control, pre-pregnancy training, pre- and during-pregnancy training, and during-pregnancy training. The HIIT protocol was performed by the mothers. Pre-pregnancy training consisted of a 6-week program (5 sessions/week) including 1-minute running intervals at 80–95% of maximal running speed with active recovery periods. During-pregnancy training was performed from gestational day 1 to day 19 at an intensity of 80–90% of maximal running speed. On postnatal day 60, offspring were classified according to their mothers’ training groups, and one male and one female offspring were randomly selected from each litter. Following left ventricular tissue collection, protein levels of VEGF, ANGPT1, and ANGPT2 were measured ELISA. Data were analyzed using Two-way ANOVA followed by Tukey’s post hoc test.

Results: Maternal physical activity altered the expression of cardiac angiogenic factors in the offspring. In the pre- and during-pregnancy training group, ANGPT1 expression was significantly higher in male offspring than in female offspring (P = 0.003). The highest levels of ANGPT2 and VEGF were observed in the pre- and during-pregnancy training group. VEGF expression was also significantly higher in both sexes in the pre- and during-pregnancy training group and the during-pregnancy training group compared with the control group (P < 0.0001), whereas physical activity performed only before pregnancy had no significant effect on VEGF expression.

Conclusion: Maternal high-intensity interval training regulated cardiac angiogenic factors in the offspring in a manner dependent on the timing of the intervention and, to some extent, offspring sex. The greatest effect was observed when maternal physical activity was initiated before pregnancy and continued throughout gestation, highlighting the importance of exercise timing for angiogenic responses in the offspring heart. These findings support the potential role of maternal exercise as a preventive strategy for the developmental programming of cardiovascular health in the offspring.