• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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 occurs. Here we show that morphological changes resulting in closure of the DA in mice are virtually identical to those observed in larger mammals, including humans, 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 fails 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 that triggers ductal closure is sensed through the EP4 receptor. In contrast, 5% of EP4(-/-) mice of mixed genetic background 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.

Pubmed ID: 9363893

Authors

  • Nguyen M
  • Camenisch T
  • Snouwaert JN
  • Hicks E
  • Coffman TM
  • Anderson PA
  • Malouf NN
  • Koller BH

Journal

Nature

Publication Data

November 6, 1997

Associated Grants

None

Mesh Terms

  • Animals
  • Animals, Newborn
  • Dinoprostone
  • Ductus Arteriosus
  • Ductus Arteriosus, Patent
  • Female
  • Fetus
  • Indomethacin
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Models, Biological
  • Mutation
  • Pregnancy
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype