Influence of exercise training on e-NOS expression, nitric oxide production and mitochondrial function in the human placenta

A regular regimen of weight-bearing exercise throughout pregnancy has been shown to improve placental growth. The goal of this study was to determine the effects of aerobic exercise training during the second half of pregnancy on e-NOS expression, nitric oxide production and mitochondrial function in human placenta. This was a randomized, controlled clinical trial of 20 healthy primigravid women between 16 and 20 weeks' gestation. The pregnant women who were assigned to the exercise group received a supervised aerobic exercise program of 60 min sessions, three times a week. A heavy mitochondrial fraction was isolated from human placental tissue by differential centrifugation. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine e-NOS expression. Respiratory rates were determined by high resolution respirometry in placenta mitochondria from control and exercised women. Flow cytometry assays were carried out to measure mitochondrial membrane potential and superoxide levels. Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p=0.05). Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p=0.05). Hydrogen peroxide production and the activity of mitochondrial respiratory complexes were also measured. Mitochondria from exercised women maintained the respiratory function and a good level of polarization. Mitochondrial O₂ -levels and H₂O₂ production rate were decreased by 6% and 26% respectively in placental mitochondria from exercised women. Activity of complex I-III of the mitochondrial respiratory chain was increased by 29% in human placental mitochondria from exercised women. Also, significant increases of 45% and 21% were observed in complexes II-III and in complex IV respectively in placenta mitochondria from exercised women. Moderate exercise can improve mitochondrial function, e-NOS expression and NO production and decrease reactive oxygen species generation at the mitochondrial respiratory chain in human placenta mitochondria.