INDICATORS OF DELAYED MATURATION OF RAT-HEART TREATED PRENATALLY WITHDEXAMETHASONE

We investigated the effects of prenatal dexamethasone treatment on ind icators of cardiac maturation: heart weight/body weight ratios, myosin heavy chain (MHC) expression, cell proliferation, and extracellular m atrix. We administered dexamethasone, a synthetic glucocorticoid (appr oximately 48 mu g/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 w ere collected from neonatal rats (12-24 h after birth). The prenatal d examethasone treatment produced smaller pups with larger heart/body we ight ratios, accompanied by a higher proliferative index and a reducti on in extracellular matrix in the ventricles (with lowest values in th e septal region) compared with control pups. We also report that, alth ough there were no sex differences in body mass or heart and heat/body weight ratios, females had a greater proportion of cells synthesizing DNA in the heart. In addition, ventricles of male pups treated with d examethasone contained lower levels of alpha-MHC mRNA, as reflected in a sex by treatment interaction. The changes in each parameter are con sistent with delayed maturation. Our findings suggest that exposure to excess glucocorticoids in utero can affect cardiac development in pot entially detrimental ways and that assessment of cardiac function shou ld be closely monitored when such circumstances arise.