Antenatal betamethasone is widely used in Australia to mature the fetal lung in complicated pregnancies; however, the information regarding its effect on other developing organs including the heart is inconclusive. We aimed to understand the molecular changes underlying the impact of maternal betamethasone administration on neonatal heart development.
Pregnant ewes received either saline (n=14) or betamethasone (BETA, 12 mg, n=12) intramuscular injections at 138 and 139 days of gestation (dG, term=150 dG). Lambs were delivered by Caesarean section at 140 dG and ventilated for 45 min before humane killing and tissue collection. Cardiac protein expression and hormone concentrations were determined in the left ventricle (LV) via Western blot and LC-MS/MS, respectively. Data were analysed by two-way ANOVA (P<0.05 was considered significant).
BETA downregulated cortisol (P<0.0001), 11-deoxycortisol (P<0.0001), corticosterone (P=0.0002), estradiol (P=0.0200) and thyroxine (T4, P<0.0001), but upregulated triiodothyronine (T3, P<0.0001) concentrations in the neonatal heart. BETA downregulated glucocorticoid receptor (GR) isoforms GRα-A (P<0.0001) and 11βHSD-2 (P=0.0253), but upregulated GRβ (P=0.0244) compared to neonatal hearts from saline treated ewes. Cardiac protein expression of IGF1R (P=0.0005) and PCNA (P=0.0017), markers of cardiac growth and proliferation, were downregulated in BETA. Cardiac CD36 (P=0.0208), a marker of fatty acid uptake, was also downregulated in BETA.
Our data suggests that BETA exposure during late gestation downregulated concentrations of multiple steroid hormones, and reduced protein abundance of GRα-A, IGF1R, and PCNA, all of which may alter heart development and program the individual for susceptibility to cardiovascular disease in adulthood.