Maternal exercise upregulates mitochondrial gene expression and increases enzyme activity of fetal mouse hearts

Abstract

Maternal exercise during pregnancy has been shown to improve the long‐term health of offspring in later life. Mitochondria are important organelles for maintaining adequate heart function, and mitochondrial dysfunction is linked to cardiovascular disease. However, the effects of maternal exercise during pregnancy on mitochondrial biogenesis in hearts are not well understood. Thus, the purpose of this study was to test the hypothesis that mitochondrial gene expression in fetal myocardium would be upregulated by maternal exercise. Twelve‐week‐old female C57BL/6 mice were divided into sedentary and exercise groups. Mice in the exercise group were exposed to a voluntary cage‐wheel from gestational day 1 through 17. Litter size and individual fetal weights were taken when pregnant dams were sacrificed at 17 days of gestation. Three to four hearts from the same group were pooled to study gene expression, protein expression, and enzyme activity. There were no significant differences in litter size, sex distribution, and average fetal body weight per litter between sedentary and exercised dams. Genes encoding mitochondrial biogenesis and dynamics, including nuclear respiratory factor‐1 (Nrf1), Nrf2, and dynamin‐related GTPase termed mitofusin‐2 (Mfn2) were significantly upregulated in the fetal hearts from exercised dams. Cytochrome c oxidase activity and ATP production were significantly increased, while the hydrogen peroxide level was significantly decreased in the fetal hearts by maternal exercise. Our results demonstrate that maternal exercise initiated at day 1 of gestation could transfer the positive mitochondrial phenotype to fetal hearts.

Exercise effects on physiological function during aging

“…Similar beneficial effects of regular exercise have been reported for young and old mice with ablation of PGC-1α, when hyper-fragmentation of mitochondrial networks was observed in aged relative to young animals, and exercise training normalized mitochondrial network structure in wild, but not in PGC-1α KO animals [50] or in human subjects [51]. The beneficial effects of exercise on mitochondrial dynamics is not limited to skeletal muscle, but also includes brains [29,52,53] and fetal hearts from exercised dams [54], while other organs have not been studied.…”

Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes

“…Our results suggest that maternal exercise may improve the capacity to maintain redox balance in the fetal heart. Results from recent studies support this notion, showing that maternal exercise resulted in increased eNOS and extracellular SOD expression in vascular smooth muscle cells, increased mitochondrial enzymatic activity, and decreased ROS in fetal cardiovascular tissues [204,205].…”

SIRT1 in forebrain excitatory neurons produces sexually dimorphic effects on depression-related behaviors and modulates neuronal excitability and synaptic transmission in the medial prefrontal cortex

“…The cDNA was generated using the High-Capacity cDNA Reverse Transcription Kit (ThermoFisher, Waltham, MA) [34] and processed for real-time PCR quantification using the QuantStudio 3 real-time PCR system (ThermoFisher, Waltham, MA). The primer sequences used for amplification of SIRT1 and the genes involved in mitochondrial biogenesis and dynamics were as follows: SIRT1 exon 4, forward-5′-GATGCTGTGAAGTTACTGCAGGAGTG-3′, reverse-5′-GAGGGTCTGGGAGGTCTGGGAAG-3′ [35]; peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), forward-5′-TGATGTGAATGAC TTGGATACAGACA-3′, reverse-5′-GCTCATTGTTGTA CTGGTTGGATATG-3′; mitofusin 1 (Mfn1), forward-5′-GCAGACAGCACATGGAGAGA-3′, reverse-5′-GATCC GATTCCGAGCTTCCG-3′; mitofusin 2 (Mfn2), forward-5′-TGCACCGCCATATAGAGGAAG-3′, reverse-5′-TC TGCAGTGAACTGGCAATG-3′; mitochondrial fission 1 protein (Fis1), forward-5′-CAAAGAGGAACAGCGG GACT-3′, reverse-5′-ACAGCCCTCGCACATACTTT-3′; dynamin-related protein 1 (Drp1), forward-5′-ATGCCAG CAAGTCCACAGAA-3′, reverse-5′-TGTTCTCGGGCAG ACAGTTT-3′ [36]; β-tubulin, forward-5′-AGCAACA TGAATGACCTGGTG-3′, reverse-5′-GCTTTCCCTAAC CTGCTTGG-3′.…”