16 Skeletal muscle microvascular architecture is unaltered in hypoxic fetal sheep

Abstract Abstract: Introduction Late gestation fetal sheep with placental insufficiency-induced fetal growth restriction (PI-FGR) have reduced vascularity and proportions of slow-twitch oxidative myofibers in tibialis anterior (TA) muscle. Sustained experimental hypoxemia in late gestation, a feature of PI-FGR, limits glucose utilization and oxidation and lowers anabolic hormones, yet does not reduce fetal weight or muscle mass. Objective We hypothesized that sustained hypoxemia disrupts oxidative myofiber development and microvascular growth in TA muscle. Methods Pregnant ewes were assigned to control (CON; n = 5) or hypoxemia (HOX; n = 10) at ∼125 days gestation (term=149 days) for ∼9-days. Myofiber area, type, and vascularity were quantified in TA muscle using immunofluorescence and Visiopharm® software. Data are expressed as mean±SD. Student’s t-test was used; P<0.05 was significant. Results Fetal PaO2 was 15% lower in HOX than CON (14.9±1.7 vs. 17.5±2.8; P=0.0427), modeling the hypoxemia in PI-FGR fetuses. Myofiber proportion, size, vascular area, arteriole and venule area, capillary area, and capillary to myofiber ratios were similar between groups. Conclusions In contrast to the PI-FGR fetus, sustained late gestation hypoxemia does not alter myofiber size, vascular architecture, or oxidative myofiber proportion in TA muscle. Thus, reduced myofiber and vascular development in the PI-FGR fetus may be caused by more severe or prolonged hypoxemia, or secondary to other factors following limited nutrient utilization and growth restriction. Alternatively, the absence of myofiber or vascular effects in response to hypoxemia may reflect fetal mechanisms to defend its oxidative metabolism and growth. (Supported by NIH R01-DK108910 and HD709404)