The prostaglandin receptor EP4 triggers remodelling of the cardiovascular system at birth

My Trang Nguyen, Todd Camenisch, John N. Snouwaert, Elizabeth Hicks, Thomas M. Coffman, Page A.W. Anderson, Nadia N. Malouf, Beverly H. Koller

Research output: Contribution to journalArticlepeer-review

281 Scopus citations

Abstract

Survival of newborn placental mammals depends on closure of the ductus arteriosus (DA), an arterial connection in the fetus which directs blood away from the pulmonary circulation and towards the placenta where oxygenation occurs1. Here we show that morphological changes resulting in closure of the DA in mice are virtually identical to those observed in larger mammals, including humans2, and that maintenance of the DA in the open, or patent, state in fetal mice is dependent on prostaglandin synthesis. This requirement is absent in mice lacking the prostaglandin E2 EP4 receptor (EP4(-/-) mice). In EP4(-/-) mice of the 129 strain, remodelling of the DA falls to occur after birth, resulting in a left-to-right shunt of blood and subsequently in death. This suggests that the neonatal drop in prostaglandin E2 (refs 3-7) that triggers ductal closure is sensed through the EP4 receptor. In contrast, 5% of EPa(-/-) mice of mixed genetic hackground survive, and selective breeding of these mice leads to a 21% survival rate, suggesting that alleles at other loci can provide an alternative mechanism for ductal closure.

Original languageEnglish (US)
Pages (from-to)78-81
Number of pages4
JournalNature
Volume390
Issue number6655
DOIs
StatePublished - Nov 6 1997

ASJC Scopus subject areas

  • General

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