Little is known about the normal developmental and endocrine regulation of mitochondria in skeletal muscle before term despite their essential role in meeting the increased postnatal energy requirements. Skeletal muscle is a major site of glucose uptake and skeletal muscle mitochondrial dysfunction arising before birth may increase risk of metabolic abnormalities in adulthood as altered muscle structure and mitochondrial function have been observed in diabetic patients, as well as in adults growth-restricted in utero. This project aims to determine whether there are developmental changes in mitochondrial function in ovine fetal skeletal muscle during late gestation and the extent to which they depend on the normal maturational increases in cortisol and triiodothyronine (T3) concentrations. Mitochondrial respiratory activity and oxidative stress will be assessed in skeletal muscles of sheep fetuses during late gestation after cortisol infusion and fetal thyroidectomy and compared to appropriate controls. Our hypothesis is that mitochondrial function will change in a hormone-dependent manner towards term. An increased understanding of this developmental regulation has implications for neonatal viability and the early life programming of adult health.
Funding: Wellcome Trust