Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring

Abstract

It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2′-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2′-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear.

Antioxidant and Adaptative Response Mediated by Nrf2 during Physical Exercise

“…Furthermore, exercise-related epigenetic changes extend beyond the individuals who engage in exercise. A study in rats descended from parents that participated in a treadmill-race training protocol, 20 min daily, five days a week, for 22 days prior to mating, had a better spatial development, as well as better DNA global methylation in the hippocampus compared with sedentary rats, suggesting a link between the pre-conceptional physical exercise of their progenitors and the improvement of the cognitive capacity of their descent, possibly related with the epigenetic programming in the hippocampus [58]. For these and other reasons, it is suggested that physical exercise be carried out at all life stages, taking into consideration the capacities or even the limitations of each individual, and that physical exercise should form part of the individual’s lifestyle.…”

Multigenerational effects of paternal spatial training are lasting in the F1 and F2 male offspring

“…What the research literature refers to is the transgenerational transmission of the effects of paternal experiences to offspring. Nevertheless, there are also conflicting results (Yeshurun et al , 2017; Mega et al , 2018; Spindler et al , 2019; Hoffmann et al , 2020). The results of these studies showed that in some cases, paternal environmental enrichment did not positively affect cognitive behaviors and neurobiologic factors in their offspring.…”

“…The present study did not use any physical exercise or enriched cages. In contrast, some conflicting studies investigated the effects of paternal high-intensity physical exercise using a treadmill (Mega et al , 2018; Spindler et al , 2019) or paternal environmental enrichment by environmentally enriched cages (Yeshurun et al , 2017; Hoffmann et al , 2020) on behavior and neurobiologic factors of their offspring.…”

Global DNA Methylation in the Limbic System of Cattle

“…Global DNA methylation levels less than 1% are not uncommon for brain tissues. Reports of global DNA methylation in the hippocampus have ranged from >0.01% to 1.15% across rat studies using the same global quantification kit as the current study [ 18 , 19 ]. We found that half of our animals had global DNA methylation levels less than 1.15% in the hippocampus.…”