Effect of gestational age, corticosteroids, and birth on expression of prostanoid EP receptor genes in lamb and baboon ductus arteriosus

The aim of this study was to determine the effect of corticosteroids, gestational age, and birth on the expression of genes encoding prostanoid receptors in the lamb and baboon ductus arteriosus. The ductus arteriosus was obtained from 34 lambs and eight baboons, including chronically instrumented fetuses of both species exposed to either corticosteroid or vehicle. Expression of prostanoid receptor genes was quantified using Northern blot analysis relative to each of two housekeeping genes. Expression of both the EP₃ and EP₄, receptor genes was detected in lamb ductus and the level of expression of both genes was unaffected by corticosteroids. Expression of the EP₄ receptor gene was lower in the ductus obtained from term lambs compared with preterm lambs and was lower still in neonatal animals, whereas no variation was observed in EP₃ receptor gene expression. Expression of the EP₄ receptor gene was also confirmed in fetal baboon ductus arteriosus, and maternal administration of corticosteroid did not reduce EP₄ receptor gene expression in the baboon. We conclude that advancing gestational age and birth may inhibit prostaglandin E₂-mediated relaxation of the ductus through a corticosteroid-independent reduction in EP₄ receptor gene expression.