Glucocorticoids are routinely administered to pregnant women at risk of pre-term delivery to mature fetal organs and improve neonatal survival. Here, we tested the hypotheses that (i) antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance fetal heart maturation and (ii) this would depend on maternal GR genotype. Female GR+/- and GR+/+ mice were crossed with GR+/- males to generate GR+/+ and GR+/- fetuses. GR+/- intercrosses also generated GR-/- (glucocorticoid-resistant controls). Dexamethasone (100 µg/kg/day) or vehicle was administered in the drinking water of pregnant dams from E12.5 (n = 3–6/group), 2d prior to the initiation of fetal glucocorticoid production. In utero high frequency ultrasound was performed at E15.5. Dexamethasone treatment of GR+/+ dams did not affect myocardial performance index (MPI), a measure of systolic and diastolic function, in either GR+/- or GR+/+ fetuses. However, compared to vehicle, dexamethasone treatment of GR+/- dams decreased MPI (indicating improved cardiac function) in their GR+/- fetuses (mean ± SEM: vehicle = 0.746 ± 0.020, dex = 0.620 ± 0.028; P < 0.01, n = 13–16) with no effect on MPI in their GR+/+ fetuses (mean ± SEM: vehicle = 0.713 ± 0.044, dex = 0.687 ± 0.082, n = 4–7). Examination of the influence of maternal genotype showed elevated MPI in GR+/- fetuses in GR+/- dams compared to GR+/+ dams (mean ± SEM: GR+/- dams = 0.769 ± 0.027, GR+/+ dams = 0.585 ± 0.075, n = 4), which was reversed by dexamethasone treatment (2-way ANOVA interaction P ≤ 0.01). Precocious GR activation therefore improves fetal heart function, but only in GR+/- fetuses from GR+/- dams, suggesting fetal heart maturation is dependent on both fetal and maternal factors. Fetal factors could include reduced GR density in GR+/- mice and maternal factors may include the higher circulating plasma levels of glucocorticoid in GR+/- mice.
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