Maternal vitamin A alters gene profiles and structural maturation of the rat ductus arteriosus

Abstract

Retinoic acid (RA), a metabolite of vitamin A, has been proposed to regulate vascular remodeling and reactivity of the ductus arteriosus (DA). Using rat Affymetrix GeneChips, we found that a considerable number of genes in DA varied their expression levels in accordance with developmental mode: namely, preterm-, term-, and postnatal-dominant clusters. Among a total of 8,740 probe sets, maternal vitamin A administration (MVA) changed the expression levels of 91 genes (116 probe sets) >2.5-fold. About half of preterm- and term-dominant genes responded to MVA, whereas only 5% of postnatal-dominant genes responded to MVA, indicating that fetal-dominant genes were susceptible to RA signals. The expression levels of 51 genes in MVA-treated DA at preterm were similar to the expression levels in nontreated DA at term, indicating that the global gene profile at preterm resembled that of the control animal at term. We observed neointima formation in MVA-treated DA at preterm in accordance with upregulation of fibronectin and hyaluronic acid, whereas it was rarely observed in nontreated DA at preterm. Five fetal cardiac myofibrillar genes were also upregulated in MVA-treated in vivo DA, whereas they were developmentally downregulated in nontreated DA. The present study indicates that MVA-mediated alteration in gene profile was associated with early structural maturation of DA, although MVA-mediated maturation may differ from normal vascular remodeling of DA.