Slow-twitch oxidative myofiber proportions and capillary number per myofiber are reduced in growth-restricted fetal sheep

Pregnancies affected with placental insufficiency and fetal growth restriction (FGR) are characterized by reduced umbilical blood flow, decreased nutrient and oxygen supply to the fetus, and impaired fetal skeletal muscle growth. Vascular development within FGR skeletal muscle has not been well described. We hypothesized that chronic placental insufficiency impairs microvascular architecture in FGR fetal skeletal muscle, resulting in decreased vascularity. We used a sheep model of placental insufficiency-induced FGR by exposing pregnant ewes to elevated temperature. Four muscles from the hindlimb were obtained in late gestation from FGR and control fetal sheep for histological and molecular analyses. The proportion of slow-twitch oxidative fibers was 22% lower in the tibialis anterior (TA) and 32% lower in the extensor digitorum longus (EDL) muscles in FGR fetuses compared with controls. Total cross-sectional area was 20%-45% lower in biceps femoris (BF), TA, EDL, and soleus (SOL) muscles. The capillary number per myofiber was 34% lower in BF, 51% lower in TA, and 21% lower in SOL FGR muscles compared with controls. Capillary area was also 44% lower in the FGR TA muscle. Taken together, late gestation fetuses with placental insufficiency-induced FGR had smaller myofibers, fewer slow-twitch oxidative myofibers, and defects in angiogenesis and capillary formation.<b>NEW & NOTEWORTHY</b> Pregnancies affected by placental insufficiency-induced FGR result in fewer slow-twitch oxidative myofibers and lower capillary number per myofiber in fetal skeletal muscle by late gestation.