Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Glucocorticoid maturation of the fetal heart - implications for preterm birth and early life programming (#128)

Karen E Chapman 1 , Emma J Batchen , Jessica R Ivy , Rachel V Richardson , Adrian Thomson , Carmel M Moran , Eva A Rog-Zielinska , Gillian A Gray , Megan C Holmes
  1. University/BHF Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK

Glucocorticoids are essential to mature fetal organs and tissues in preparation for life after birth, the reason they are used clinically in pregnant women at risk of preterm delivery. Conversely, excessive prenatal exposure to glucocorticoid increases risk of cardio-metabolic disease in adulthood. We have used glucocorticoid receptor (GR) knockout mouse models to show a previously unappreciated and essential role for GR to functionally, structurally and biochemically mature the fetal heart. Experiments in primary fetal mouse cardiomyocytes suggest that this occurs, at least in part, through remodelling of mitochondria. Mitochondrial mechanisms underlie the perinatal switch in cardiomyocytes from hyperplastic growth to cell cycle exit, binucleation and hypertrophic growth. Data from our 'SMGRKO' mice, which lack GR selectively in cardiomyocytes and vascular smooth muscle, point to a delay in this switch. Prolonged cardiomyocyte proliferation in neonatal SMGRKO mice is associated with greater cardiac mass yet normal sized cardiomyocytes in adulthood. This suggests that glucocorticoid induced maturation of the fetal heart is coupled to, and at the expense of, cardiomyocyte endowment in adulthood. In vivo and in vitro (in primary mouse fetal cardiomyocytes) data relating to glucocorticoid effects upon the mouse fetal heart will be presented. Whether an alteration in the balance between glucocorticoid receptor and mineralocorticoid receptor activation may underlie differences in the effects of exogenous and endogenous glucocorticoids upon the perinatal heart will also be discussed.