Placental Klotho responses to supervised prenatal exercise: findings from the PLACENTRAINING study

Background: Regular exercise during pregnancy improves maternal and neonatal outcomes; however, the molecular pathways underlying placental adaptations to prenatal exercise remain poorly understood. Klotho is a cytoprotective protein involved in the regulation of oxidative stress, metabolic homeostasis, and cellular resilience, yet whether placental Klotho concentrations are associated with prenatal exercise has not been previously investigated. Aims: The primary aim of this study was to examine whether participation in a supervised concurrent exercise program during pregnancy is associated with placental Klotho concentrations at birth. Secondary aims were to explore potential fetal sex-specific patterns and associations between placental Klotho and selected biomarkers related to angiogenic and inflammatory pathways. Methods: Pregnant women were allocated to either a supervised concurrent exercise program or usual care. The intervention comprised combined aerobic and resistance training performed three times per week from early-mid pregnancy until birth. Placental tissue was collected at birth, and Klotho concentrations were quantified by enzyme-linked immunosorbent assay (ELISA). Secondary analyses explored potential sex-specific patterns and examined associations between placental Klotho, placental weight, and a panel of placental biomarkers. Results: Seventy-six women were included (exercise: n = 41; control: n = 35). Placental Klotho concentrations were significantly higher in the exercise group, with an adjusted mean difference of approximately 101 pg/mL (p = 0.001; partial η 2 = 0.164). This effect was consistent across fetal sex, with no significant exercise-by-sex interaction. Several placental biomarkers were independently associated with Klotho, suggesting a potential relationship with angiogenic and inflammatory signaling pathways. Conclusions: Participation in a supervised concurrent exercise program during pregnancy is associated with higher placental Klotho concentrations at birth, irrespective of fetal sex. These findings provide novel insight into molecular pathways potentially involved in placental adaptations associated with prenatal exercise and reinforce the concept of the placenta as an exercise-responsive organ during pregnancy. Keywords: Concurrent training; Exerkines; Oxidative stress; Pregnancy; Placental function