Maternal exercise enhances fetal bone development

Introduction: During development, fetal movement provides mechanical forces necessary for proper skeletal morphogenesis. Clinical conditions that limit fetal movement (i.e., fetal akinesia) can impair bone development and cause skeletal deformities. Based on this, we hypothesized that extra-embryonic mechanical stimulation could enhance fetal skeletal development. The goal of this project was to determine if maternal wheel running exercise could serve as a non-invasive, in utero intervention, capable of providing extra-embryonic mechanical stimulation.

Materials and

Methods: To mechanically stimulate embryos in utero, we performed maternal wheel running exercise. Briefly, female C57BL/6 mice were individually housed and acclimated to home cage running wheels for at least 2 weeks. Acclimated female mice were mated with male C57BL/6 mice, then housed without wheels until embryonic day (E) 13.5. At E13.5, pregnant mice were either re-housed with wheels from E13.5 to E16.5, inclusive (Ad Libitum), or subjected to 1 hour of daily supervised wheel running during the same period (Supervised). Control groups with locked wheels were included for both conditions (Jammed). Pregnant mice ran more consistently using supervised running (Fig 1A); therefore, we used this approach for future analyses.

Results, Conclusions, and Discussions: Embryos were harvested from Supervised and Jammed groups at E17.5 to quantify bone morphogenesis and placental transport efficiency. Forelimb bone morphogenesis was quantified using microcomputed tomography (voxel size = 3 µm, x-ray tube potential = 70 kVp, x-ray intensity = 145 µA, integration time = 300 ms). Embryos from exercised mothers showed increased humerus bone collar length, indicating that maternal exercise has osteogenic effects on developing embryos (Fig 1B).
Intrauterine growth is also influenced by placental transport efficiency. To assess whether maternal exercise influences placental transport, we quantified the standard measurement of fetus weight to placental weight ratio (FW:PW). We observed no significant differences in FW:PW in response to Supervised maternal exercise (Fig 1C).
Together, our results demonstrate that maternal wheel running exercise promotes bone formation in fetal skeletons, independent of placental transport. Future studies will elucidate the underlying cellular and molecular mechanisms. Ultimately, this research may indicate maternal exercise as a non-invasive, in utero intervention for skeletal deformities caused by limited fetal movement. Additionally, this work establishes maternal exercise as a model for studying developmental mechanobiology in vivo.

Acknowledgements (Optional): This work was supported by NIH K12 GM081259-16.