Indicators of delayed maturation of rat heart treated prenatally with dexamethasone.

Abstract

We investigated the effects of prenatal dexamethasone treatment on indicators of cardiac maturation: heart weight/body weight ratios, myosin heavy chain (MHC) expression, cell proliferation, and extracellular matrix. We administered dexamethasone, a synthetic glucocorticoid (approximately 48 microg/d, 3-wk slow release pellets), to pregnant rats (n = 8) beginning at 17 d postconception. Control dams were unmanipulated (n = 8). After approximately 4-5 d of dexamethasone exposure, hearts were collected from neonatal rats (12-24 h after birth). The prenatal dexamethasone treatment produced smaller pups with larger heart/body weight ratios, accompanied by a higher proliferative index and a reduction in extracellular matrix in the ventricles (with lowest values in the septal region) compared with control pups. We also report that, although there were no sex differences in body mass or heart and heart/body weight ratios, females had a greater proportion of cells synthesizing DNA in the heart. In addition, ventricles of male pups treated with dexamethasone contained lower levels of alpha-MHC mRNA, as reflected in a sex by treatment interaction. The changes in each parameter are consistent with delayed maturation. Our findings suggest that exposure to excess glucocorticoids in utero can affect cardiac development in potentially detrimental ways and that assessment of cardiac function should be closely monitored when such circumstances arise.