Developmental programming in response to intrauterine growth restriction impairs myoblast function and skeletal muscle metabolism.


Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.

Adaptation, Physiological, Biomarkers, Catecholamines, Female, Fetal Development, Fetal Growth Retardation, Fetal Hypoxia, Humans, Hypoglycemia, Muscle Development, Muscle, Skeletal, Myoblasts, Skeletal, Placental Insufficiency, Pregnancy, Prenatal Exposure Delayed Effects
D. T. Yates, A. R. Macko, M. Nearing, X. Chen, R. P. Rhoads, and S. W. Limesand, “Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism,” Journal of Pregnancy, vol. 2012, Article ID 631038, 10 pages, 2012. doi:10.1155/2012/631038