Defining a Role for Prostanoid Receptor EP4 in the Developmental Programming of the Ductus Arteriosus

Abstract

The ductus arteriosus (DA) is a muscular artery which helps to define the fetal pattern of the circulatory system. After birth, the DA undergoes muscular constriction and remodeling which establish the adult division between the pulmonary and systemic circulation. Fetal DA patency requires acute vasodilatory signaling via the prostaglandin (PGE2) receptor EP4. However, in humans and mice, disrupted PGE2-EP4 signaling in utero causes unexpected persistent patency of the DA (PDA) after birth, suggesting another chronic role for EP4 during development. It is likely that sustained PGE2 signaling via EP4 is responsible for directing the proper development of the DA to enable its closure after birth. This is mediated through highly ordered developmental processes, likely representing a developmental program that is heretofore an unstudied paradigm for DA formation and function.