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This study therefore investigated the effects of antenatal betamethasone on cardiac development in near\u2010term lambs, using tissues collected from a cohort of ewes with mild experimentally induced asthma. Pregnant ewes received two doses of either saline (Saline) or betamethasone (Betamethasone, intramuscular, 11.4\u00a0mg) given 24\u00a0h apart, before delivery at 140\u00a0days of gestation (term\u00a0=\u00a0150days of gestation). Cardiac protein expression and hormone concentrations in the left ventricle were analysed using western blot and LC\u2013MS\/MS, respectively. Fetal and neonatal heart rate and blood pressure were higher in Betamethasone compared to Saline lambs. Betamethasone lambs had lower cardiac concentrations of cortisol, corticosterone, oestradiol, progesterone and thyroxine but a higher triiodothyronine. The protein ratio of glucocorticoid receptor GR\u03b2:GR\u03b1\u2010A was higher in the hearts of Betamethasone compared to Saline. Additionally, the expression of insulin\u2010like growth factor 1\u00a0receptor (a marker of cardiac proliferative capacity), proliferating cell nuclear antigen (a marker of DNA replication) and the fatty acid transporter CD36 were lower in Betamethasone lambs. These findings suggest that antenatal betamethasone may disrupt normal heart development by altering glucocorticoid receptor isoform expression and reducing cardiac exposure to glucocorticoid and sex hormones. Consequently, this leads to decreased expression of markers associated with cardiac growth and fatty acid uptake. These alterations in heart development caused by antenatal corticosteroids exposure may increase the risk of cardiovascular disease later in life if these changes persist into adulthood.<\/jats:p>","DOI":"10.1113\/ep093025","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T19:23:21Z","timestamp":1757013801000},"page":"988-1007","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antenatal betamethasone impairs markers of cardiac development and function in near\u2010term lambs"],"prefix":"10.1113","volume":"111","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 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki L.","family":"Clifton","sequence":"additional","affiliation":[{"name":"Pregnancy and Development Group, Mater Research Institute University of Queensland South Brisbane  Brisbane QLD 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 &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Wiese","sequence":"additional","affiliation":[{"name":"Centre for Pharmaceutical Innovation, Clinical &amp; Health Sciences University of South Australia  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-3004","authenticated-orcid":false,"given":"Kathryn L.","family":"Gatford","sequence":"additional","affiliation":[{"name":"Robinson Research Institute University of Adelaide  Adelaide SA Australia"},{"name":"School of Biomedicine University of Adelaide  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3594-1455","authenticated-orcid":false,"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 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 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2020.104679"},{"key":"e_1_2_10_3_1","first-page":"1","article-title":"Elevated cortisol concentration in preterm sheep fetuses impacts heart development","author":"Amanollahi R.","year":"2025","journal-title":"Experimental Physiology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd12020036"},{"key":"e_1_2_10_5_1","unstructured":"Antenatal Corticosteroid Clinical Practice Guidelines Panel. 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