Maternal exercise before and during pregnancy protects against genotoxicity and promotes offspring hippocampal health in mice prenatally exposed to high fructose

The fetal brain is susceptible to programming effects during pregnancy, potentially leading to long-term consequences for offspring's cognitive health. Fructose intake is thought to adversely affect fetal brain development, whereas physical exercise before and during pregnancy may be protective. Therefore, this study aimed to assess biochemical and genotoxic changes in maternal hippocampi and behavioral, genotoxic, and biochemical alterations in offspring hippocampi. Seventy female mice were exposed to fructose (20%/L) and/or voluntary physical exercise (VPE) pre-pregnancy for eight weeks, and then mated and exposure was continued until weaning. Offspring were evaluated at 60 days old using behavioral test, genotoxic and biochemical markers. Fructose induced long-term memory impairment in male offspring, which was alleviated by VPE. VPE mitigated DNA damage from maternal fructose consumption in both maternal and offspring hippocampi in female offspring, VPE increased levels of APE-1, NRF2, and CREB proteins, whereas in males, OGG1 levels upregulate. Fructose consumption led to oxidative stress and antioxidant defense alterations in offspring, while VPE mitigated these effects. Telomere shortening was observed in male offspring from mothers who consumed fructose during pregnancy. Our findings suggest that exposure to fructose during (pre)pregnancy and lactation has adverse effects on offspring's hippocampi later in life, and VPE has a protective effect. Overall, the study underscores the significance of maternal dietary and physical habits on long term offspring health, with an emphasis on implications for adult cognitive function.