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 analysis. 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 to 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 to 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.