Development and thyroid hormone dependence of skeletal muscle mitochondrial function towards birth

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. Abstract 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.

In utero substrate restriction by placental insufficiency or maternal undernutrition decreases optical redox ratio in foetal perirenal fat

“…Mitochondrial uncoupling, induced by cold exposure of BAT, leads to an increase in UCP1 [74] and mitochondrial uncoupling also results in an increase in optical redox ratio, which reflects elevated electron flux through electron transport chain [42, 43]. Prepartum increases in foetal circulating cortisol and thyroid hormone may also play a role in this process [75].…”

Developing mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

“…Mammary tissue was collected from female sheep aged less than one year that were submitted to the diagnostic veterinary anatomic pathology service of the Department of Veterinary Medicine, University of Cambridge. Additionally, mammary tissue was obtained post mortem from 2 day old – 9.5 months old Welsh mountain ewes studied for other research purposes (Davies et al, 2020) and euthanased under the Animals (Scientific Procedures) Act 1986. The Ethics and Welfare Committee of the Department of Veterinary Medicine, University of Cambridge, approved the study plan relating to the use of ovine post mortem material for the study of mammary gland biology (reference: CR223).…”

Emerging views of how changes in T3 influence prenatal metabolic maturation

“…In a recent issue of the Journal of Physiology , Davies et al . (2020) evaluated the influence of thyroid hormones on the development and proliferation of skeletal muscle mitochondria during the perinatal period. Their findings showed that although T 3 is positively correlated with mitochondrial density and mitochondrial OXPHOS capacity, the latter is upregulated postnatally, thus revealing a temporal discrepancy.…”