Maternal Exercise Rescues Fetal Akinesia-Impaired Joint and Bone Development

Fetal movements exert mechanical forces that shape the developing skeleton. Conditions that impair fetal movement can cause skeletal defects, but interventions are limited. Here, we show that maternal wheel running exercise regulates fetal skeletal development in mice. In wild-type fetuses, maternal exercise stimulated joint morphogenesis and bone development. These changes could not be fully explained by altered placental transport. Therefore, we next evaluated the effects of maternal exercise in the Splotch-delayed (Sp^d) mouse model of fetal akinesia, which features intact maternofetal communication, but homozygous mutants lack contractile limb skeletal muscle. Maternal exercise substantially rescued fetal akinesia-impaired joint and bone development and prevented disuse-induced resorption of the deltoid tuberosity. Further, bioreactor mechanical stimulation of explanted Sp^d limbs, which remove systemic factors, similarly stimulated joint morphogenesis. Together, these findings identify maternal exercise as a regulator of fetal skeletal development, provide a platform for studying skeletal developmental mechanobiology, and suggest potential therapeutic implications for maternal exercise in skeletal conditions caused by impaired fetal movement.