Real supermodels wear wool: Summarizing the impact of the pregnant sheep as an animal model for adaptive fetal programming

Implications • Intrauterine growth restriction (IUGR) continues to be a global epidemic that is associated with high early-life mortality rates and greater risk for developing metabolic disorders that lower length and quality of life in affected individuals. • Fetal programming of muscle growth and metabolic function associated with IUGR is often comparable among nonlitter bearing mammalian species, which allows much of the information learned in domestic animal models to be applicable to humans (and other animals). • Recent studies in sheep models of IUGR have begun to uncover the molecular mechanisms linking adaptive fetal programming and metabolic dysfunction. • Targets of adaptive fetal programming indicated by sheep studies include adrenergic and inflammatory pathways that regulate skeletal muscle growth and glucose metabolism. Adaptive changes in these pathways represent potential focus areas for prenatal interventions or postnatal treatments to improve outcomes in IUGR-born offspring.