Amanollahi, R.Meakin, A.S.Holman, S.L.Clifton, V.L.Thornburg, K.L.Wiese, M.D.Gatford, K.L.Lock, M.C.Morrison, J.L.2025-10-302025-10-302025Experimental Physiology, 2025; EP093025-1-EP093025-200958-06701469-445Xhttps://hdl.handle.net/2440/148072OnlinePubl. Available 4 September 2025Antenatal corticosteroids are commonly administered to promote fetal lung maturation; however, their impact on heart development is not well understood. This study therefore investigated the effects of antenatal betamethasone on cardiac development in near-term 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 mg) given 24 h apart, before delivery at 140 days of gestation (term = 150days of gestation). Cardiac protein expression and hormone concentrations in the left ventricle were analysed using western blot and LC–MS/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 GRβ:GRα-A was higher in the hearts of Betamethasone compared to Saline. Additionally, the expression of insulin-like growth factor 1 receptor (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.en© 2025 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.antenatal corticosteroid; cardiac hormones; cardiac metabolism; fetal development; glucocorticoid; sheepJournal article10.1113/EP093025859275Clifton, V.L. [0000-0002-4892-6748]Gatford, K.L. [0000-0002-2823-3004]