Abstract
Key points Skeletal muscle energy requirements increase at birth but little is known regarding the development of mitochondria that provide most of the cellular energy as ATP.Thyroid hormones are known regulators of adult metabolism and are important in driving several aspects of fetal development, including muscle fibre differentiation.Mitochondrial density and the abundance of mitochondrial membrane proteins in skeletal muscle increased during late gestation. However, mitochondrial functional capacity, measured as oxygen consumption rate, increased primarily after birth.Fetal hypothyroidism resulted in significant reductions in mitochondrial function and density in skeletal muscle before birth.Mitochondrial function matures towards birth and is dependent on the presence of thyroid hormones, with potential implications for the health of pre‐term and hypothyroid infants. Birth is a significant metabolic challenge with exposure to a pro‐oxidant environment and the increased energy demands for neonatal survival. This study investigated the development of mitochondrial density and activity in ovine biceps femoris skeletal muscle during the perinatal period and examined the role of thyroid hormones in these processes. Muscle capacity for oxidative phosphorylation increased primarily after birth but was accompanied by prepartum increases in mitochondrial density and the abundance of electron transfer system (ETS) complexes I–IV and ATP‐synthase as well as by neonatal upregulation of uncoupling proteins. This temporal disparity between prepartum maturation and neonatal upregulation of mitochondrial oxidative capacity may protect against oxidative stress associated with birth while ensuring energy availability to the neonate. Fetal thyroid hormone deficiency reduced oxidative phosphorylation and prevented the prepartum upregulation of mitochondrial density and ETS proteins in fetal skeletal muscle. Overall, the data show that mitochondrial function matures over the perinatal period and is dependent on thyroid hormones, with potential consequences for neonatal viability and adult metabolic health.
Highlights
Birth is a significant metabolic challenge to the neonate
Over late gestation there was an increase in mitochondrial density and abundance of electron transfer system (ETS) and other proteins involved in oxidative ATP generation, consistent with other prepartum maturational processes known to ensure a successful transition to extrauterine life (Fowden et al 1998)
Fetal hypothyroidism induced by surgical removal of the fetal thyroid glands showed that thyroid hormones are necessary for most of the developmental changes in mitochondrial function that occur towards term
Summary
Birth is a significant metabolic challenge to the neonate It must maintain its internal environment for the first time and activate many vital processes that have little or no function in utero, including pulmonary respiration, enteral nutrition, gluconeogenesis and thermoregulation (Fowden et al 1998). Neonatal energy demands rise rapidly after birth as organs and tissues assume these new roles. The energy needed is provided as ATP, produced primarily by oxidative phosphorylation (OXPHOS) in the mitochondria, which requires and accounts for the significant increase in the rate of oxygen consumption after birth (Klein et al 1983). This, together with the fluctuations in arterial partial pressure of oxygen ( PaO2 ) during labour and the rapid rise in O2 exposure at birth, increases the risk of excessive mitochondrial superoxide production and oxidative damage to the neonatal tissues (Rogers et al 1998). Preparations for the neonatal metabolic challenges begin before birth in several of the key tissues essential for neonatal survival, but little is known regarding the normal prepartum maturation of mitochondrial function in any fetal tissue
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