Comparative analysis of ovine fetal skeletal muscle gene expression: control and intrauterine growth restriction (IUGR)

Impaired muscle growth as a result of IUGR is a major contributor to lifelong reductions in muscle mass (sarcopenia) and metabolic disease risk. We use an ovine model of chronic placental insufficiency which restricts nutrient supply from mother to fetus and results in intrauterine growth restriction. In our model of placental insufficiency and IUGR, fetal hindlimb muscles weigh less than normally-grown control fetuses and have smaller myofiber diameters. Given the frequent correlation between functional changes and transcriptional changes, we investigated the effect of chronic placental insufficiency and IUGR on fetal skeletal muscle gene expression. We found that gene expression in the skeletal muscle is significantly altered by chronic placental insufficiency. In gene ontology analysis, we found that genes involved in cell cycle regulation were most significantly affected, with downregulation of several cyclins. These observations may in part account for decreased muscle weight relative to brain weight observed in the late gestation IUGR fetus. Biceps femoris muscle from control and IUGR fetal sheep were excised at 90% of gestation. Total RNA was extracted and biotin-labeled amplified cRNA was hybridized to Affymetrix Bovine Genome Arrays.