{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:20:57Z","timestamp":1789564857316,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Research Council Future Fellowship","award":["FT170100431"],"award-info":[{"award-number":["FT170100431"]}]},{"name":"University of South Australia President\u2019s Scholarship","award":["FT170100431"],"award-info":[{"award-number":["FT170100431"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Understanding hormonal and molecular changes during the transition from preterm to near-term gestation is essential for investigating how pregnancy complications impact fetal heart development and contribute to long-term cardiovascular risks for offspring. This study examines these cardiac changes in fetal sheep, focusing on the changes between 116 days (preterm) and 140 days (near term) of gestation (dG, term = 150) using Western blotting, LC-MS\/MS, and histological techniques. We observed a strong correlation between cortisol and T3 (Triiodothyronine) in heart tissue in near-term fetuses, highlighting the role of glucocorticoid signalling in fetal heart maturation. Protein expression patterns in the heart revealed a decrease in multiple glucocorticoid receptor isoforms (GR\u03b1-A, GR-P, GR-A, GR\u03b1-D2, and GR\u03b1-D3), alongside a decrease in IGF-1R (a marker of cardiac proliferative capacity) and p-FOXO1(Thr24) but an increase in PCNA (a marker of DNA replication), indicating a shift towards cardiomyocyte maturation from preterm to near term. The increased expression of proteins regulating mitochondrial biogenesis and OXPHOS complex 4 reflects the known transition from glycolysis to oxidative phosphorylation, essential for meeting the energy demands of the postnatal heart. We also found altered glucose transporter expression, with increased pIRS-1(ser789) and GLUT-4 but decreased GLUT-1 expression, suggesting improved insulin responsiveness as the heart approaches term. Notably, the reduced protein abundance of SIRT-1 and SERCA2, along with increased phosphorylation of cardiac Troponin I(Ser23\/24), indicates adaptations for more energy-efficient contraction in the near-term heart. In conclusion, these findings show the complex interplay of hormonal, metabolic, and growth changes that regulate fetal heart development, providing new insights into heart development that are crucial for understanding pathological conditions at birth and throughout life.<\/jats:p>","DOI":"10.3390\/jcdd12020036","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T11:47:32Z","timestamp":1737460052000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Ontogeny of Fetal Cardiometabolic Pathways: The Potential Role of Cortisol and Thyroid Hormones in Driving the Transition from Preterm to Near-Term Heart Development in Sheep"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6960-7703","authenticated-orcid":false,"given":"Reza","family":"Amanollahi","sequence":"first","affiliation":[{"name":"Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6326-4797","authenticated-orcid":false,"given":"Stacey L.","family":"Holman","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-1503","authenticated-orcid":false,"given":"Melanie R.","family":"Bertossa","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2806-6274","authenticated-orcid":false,"given":"Ashley S.","family":"Meakin","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent L.","family":"Thornburg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Developmental Health, Knight Cardiovascular Institute, Bob and Charlee Moore Institute of Nutrition and Wellness, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Caroline","family":"McMillen","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Wiese","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, Clinical & Health Sciences University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell C.","family":"Lock","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8602-8519","authenticated-orcid":false,"given":"Janna L.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Health and Biomedical Innovation, UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1161\/CIRCULATIONAHA.104.528356","article-title":"Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s: Findings from the Aberdeen Children of the 1950s prospective cohort study","volume":"112","author":"Lawlor","year":"2005","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1001\/jama.2011.1331","article-title":"Gestational Age at Birth and Mortality in Young Adulthood","volume":"306","author":"Crump","year":"2011","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1097\/00004872-200018070-00002","article-title":"The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: A systematic review of the literature","volume":"18","author":"Huxley","year":"2000","journal-title":"J. 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