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dc.contributor.authorDavies, Katie L
dc.contributor.authorCamm, Emily J
dc.contributor.authorSmith, Danielle J
dc.contributor.authorMiles, Jack
dc.contributor.authorForhead, Alison J
dc.contributor.authorMurray, Andrew J
dc.contributor.authorFowden, Abigail L
dc.description.abstractPrenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.
dc.description.sponsorshipBBSRC Grant number (BBP019048/1)
dc.publisherCambridge University Press (CUP)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.titleDevelopmental programming of mitochondrial substrate metabolism in skeletal muscle of adult sheep by cortisol exposure before birth.
dc.publisher.departmentDepartment of Physiology, Development And Neuroscience
prism.publicationNameJ Dev Orig Health Dis
dc.contributor.orcidFowden, Abigail L [0000-0002-3384-4467]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P019048/1)
cam.orpheus.successThu Jul 28 15:14:15 BST 2022 - Embargo updated
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International