The switch: the role of glucocorticoids during fetal cardiomyocyte energy metabolism.

Abstract

Glucocorticoids play a crucial role in the maturation of foetal organs during pregnancy, as well as the preparation of extrauterine life and increased energy demands upon removal of the nutrient-rich placenta following birth. The administration of synthetic glucocorticoids, as either Celestone, a formulation of betamethasone acetate with betamethasone phosphate, or solely betamethasone acetate, is routine in many countries (Agnew et al. 2018). The benefits of antenatal corticosteroid treatment are vast, one of which is its ability to help with the maturation of fetal lung tissue and prevent neonatal respiratory distress syndrome in preterm babies (McGoldrick et al. 2020). Endogenously, glucocorticoids are associated with the development of the heart (Hillman et al. 2012). Cardiomyocytes undergo terminal differentiation during pregnancy, including changes to mitochondria, energy metabolism, calcium-handling, and more. Abundant literature exists on the effects of glucocorticoids on cardiomyocytes perinatally, but the direct effects of glucocorticoids, through the glucocorticoid receptor (GR), are not as well established. Furthermore, the role of synthetic glucocorticoids on thematuration of cardiomyocytes during different stages of gestation is also unknown. Elucidating the differences between endogenous and exogenous glucocorticoid administration can help clarify relationships between cardiac pathology and steroidogenesis and also provide a basis for future interventions to minimize the risk of developing cardiovascular disease, which may be influenced by synthetic glucocorticoid administration perinatally. Current research by Ivy et al. (2021), recently published in The Journal of Physiology, shows the impact of glucocorticoids on cardiomyocytes, specifically by looking at its effects on energy metabolism. This study follows a trifold experimental method to observe the effects of glucocorticoids on various levels of tissue: fetal cardiomyocytes with dexamethasone treatment depicting endogenous effects, neonatal mice with dexamethasone treatment to observe postnatal changes after birth, and pregnant dams with dexamethasone treatment to depict late-gestation effects of exogenous corticosteroids. A translational lamb model was also established to mimic the effects of synthetic corticosteroid injections.