{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:16:05Z","timestamp":1783548965159,"version":"3.55.0"},"reference-count":58,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesized that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon a glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , in neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genes. However, dexamethasone treatment of pregnant C57Bl\/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24\u00a0h later. Instead, at E17.5, fatty acid oxidation genes were downregulated by dexamethasone, as was GR itself. PGC\u20101\u03b1, required for glucocorticoid\u2010induced maturation of primary mouse fetal cardiomyocytes\n                      <jats:italic>in vitro<\/jats:italic>\n                      , was also downregulated in fetal hearts at E17.5, 24\u00a0h after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a translational sheep model of preterm birth, both GR and PGC\u20101\u03b1 were downregulated in heart. These data suggest that endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by downregulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Glucocorticoids are steroid hormones that play a vital role in late pregnancy in maturing fetal organs, including the heart.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In fetal cardiomyocytes in culture, glucocorticoids promote mitochondrial fatty acid oxidation, suggesting they facilitate the perinatal switch from carbohydrates to fatty acids as the predominant energy substrate.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Administration of a synthetic glucocorticoid in late pregnancy in mice downregulates the glucocorticoid receptor and interferes with the normal increase in genes involved in fatty acid metabolism in the heart.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In a sheep model of preterm birth, antenatal corticosteroids (synthetic glucocorticoid) downregulates the glucocorticoid receptor and the gene encoding PGC\u20101\u03b1, a master regulator of energy metabolism.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These experiments suggest that administration of antenatal corticosteroids in anticipation of preterm delivery may interfere with fetal heart maturation by downregulating the ability to respond to glucocorticoids.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp281860","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T04:11:37Z","timestamp":1631247097000},"page":"4901-4924","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Glucocorticoids regulate mitochondrial fatty acid oxidation in fetal cardiomyocytes"],"prefix":"10.1113","volume":"599","author":[{"given":"Jessica R.","family":"Ivy","sequence":"first","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-9939","authenticated-orcid":false,"given":"Roderic N.","family":"Carter","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Feng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Buckley","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Urquijo","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva A.","family":"Rog\u2010Zielinska","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Panting","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"},{"name":"School of Human Sciences The University of Western Australia  Crawley Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Hrabalkova","sequence":"additional","affiliation":[{"name":"The Centre for Reproductive Health The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Nicholson","sequence":"additional","affiliation":[{"name":"The Centre for Reproductive Health The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2703-0114","authenticated-orcid":false,"given":"Emma J.","family":"Agnew","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W.","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Yong Loo Lin School of Medicine National University of Singapore  Singapore Republic of Singapore"},{"name":"Division of Obstetrics and Gynaecology The University of Western Australia  Crawley Western Australia Australia"},{"name":"Centre for Perinatal and Neonatal Medicine Tohoku University Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Morton","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Stock","sequence":"additional","affiliation":[{"name":"The Centre for Reproductive Health The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"},{"name":"Division of Obstetrics and Gynaecology The University of Western Australia  Crawley Western Australia Australia"},{"name":"The Usher Institute The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5746-5680","authenticated-orcid":false,"given":"Caitlin","family":"Wyrwoll","sequence":"additional","affiliation":[{"name":"School of Human Sciences The University of Western Australia  Crawley Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-9407","authenticated-orcid":false,"given":"Ian G.","family":"Ganley","sequence":"additional","affiliation":[{"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-6817","authenticated-orcid":false,"given":"Karen E.","family":"Chapman","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science The Queen's Medical Research Institute The University of Edinburgh  Edinburgh UK"},{"name":"School of Human Sciences The University of Western Australia  Crawley Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"e_1_2_5_2_1","volume-title":"On the constitutional and local effects of disease of the supra\u2010renal capsules","author":"Addison T","year":"1855"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-18-0666"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-18-0077"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2013.168"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00296.2017"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.03.002"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2014-1362"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.025"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.13.1608"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP279194"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174416000477"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2016.04.250"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812671106"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-14-0025"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1079\/PNS19980017"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.05773"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2459"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2018.02.022"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2012.09.009"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60980-9"},{"key":"e_1_2_5_22_1","first-page":"240","article-title":"The clinical use of corticosteroids in pregnancy","volume":"22","author":"Kemp MW","year":"2016","journal-title":"Human Reproduction Update"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.05.007"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.10.026"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00523.2009"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-18-0152"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.134023"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10268"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00081.2008"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.013"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3181e74a14"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201603039"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-111914"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90285-L"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00391.2017"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512968112"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2008.10.003"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8945com"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0841-1"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2011.02.002"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/612089"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00027.2015"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14336"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.181"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-13-0204"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt182"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0519-0"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45171-6"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/82.13.1107"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-18-0672"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)90463-6"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00103-8"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2010.11.010"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199708000-00001"},{"key":"e_1_2_5_55_1","first-page":"3231","article-title":"Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells","volume":"142","author":"den Berg CW","year":"2015","journal-title":"Development"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2014.10.003"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.1.8600"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003782"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117817"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP281860","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP281860","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP281860","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T05:08:17Z","timestamp":1693199297000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP281860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":58,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1113\/JP281860"],"URL":"https:\/\/doi.org\/10.1113\/jp281860","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.04.30.442128","asserted-by":"object"}]},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]},"assertion":[{"value":"2021-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}