Exercise enhances placental labyrinth trophoblast development by activation of PGC-1α and FNDC5/irisin.

Placental chorion/labyrinth trophoblasts are energy demanding which is met by the mitochondrial oxidative phosphorylation. Exercise enhances placental development and mitochondrial biogenesis, but the underlying mechanisms remain poorly understood. To address, female C57BL/6 J mice were randomly assigned into two groups: a control (CON) group and an exercise (EX) group. All animals were acclimated to treadmill exercise for one week before mating, but only the EX group was subjected to daily exercise during pregnancy from embryonic day (E) 1.5 to E16.5. Placenta was collected at E18.5 for biochemical and histochemical analyses, and primary trophoblast cells were isolated from the E18.5 placenta for further analyses. Data showed the exercise during pregnancy promoted the expression of syncytiotrophoblast cell markers, indicating trophoblast cell differentiation, which was closely associated with elevated mitochondrial biogenesis and oxidative metabolism in the E18.5 placenta. In addition, exercise during pregnancy activated PGC-1α, which was associated with upregulated placental α-ketoglutarate (α-KG) and the expression of isocitrate dehydrogenases (IDHs) and ten-eleven translocations (TETs), facilitating DNA demethylation of the Pgc1a promoter. Furthermore, exercise upregulated FNDC5 expression and the secretion of its cleaved form, irisin, which is known to activate PGC-1α. These data suggest that exercise-induced activation of PGC-1α, via epigenetic modifications, is responsible for promoting mitochondrial energy metabolism and chorion/labyrinth trophoblast development.