Hypoxia induces cardiac malformations via A1 adenosine receptor activation in chicken embryos

✍ Scribed by Satish K. Ghatpande; Charles J. Billington Jr; Scott A. Rivkees; Christopher C. Wendler

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 951 KB
• Volume: 82
• Category: Article
• ISSN: 1542-0752
• DOI: 10.1002/bdra.20438

✦ Synopsis

Abstract

BACKGROUND:

The current understanding of the effects of hypoxia on early embryogenesis is limited. Potential mediators of hypoxic effects include adenosine, which increases dramatically during hypoxic conditions and activates A~1~ adenosine receptors (A~1~ARs).

METHODS:

To examine the influences of hypoxia and adenosine signaling on cardiac development, chicken embryos were studied. Real time RT‐PCR assay was used to examine the A~1~AR gene expression during embryogenesis and after siRNA‐ mediated knock down. Cell proliferation was determined by counting cell nuclei and PhosphoHistone H3 positive cells. Apoptosis was determined by TUNEL assay.

RESULTS:

A~1~ARs were found to be expressed in chicken embryos during early embryogenesis. Treatment of Hamburger and Hamilton stage 4 embryos with the A~1~AR agonist N^6^‐cyclopentyladenosine caused cardiac bifida and looping defects in 55% of embryos. Hamburger and Hamilton stage 4 embryos exposed to 10% oxygen for 6, 12, 18, and 24 h followed by recovery in room air until stage 11, exhibited cardia bifida and looping defects in 34, 45, 60, and 86% of embryos respectively. Hypoxia‐induced abnormalities were reduced when A~1~AR signaling was inhibited by the A~1~AR antagonist 1,3 dipropyl‐8‐cyclopentylxanthine or by siRNA‐targeting A~1~ARs. Hypoxia treatment did not increase apoptosis, but decreased embryonic cell proliferation.

CONCLUSIONS:

These data indicate that hypoxia adversely influences cardiac malformations during development, in part by A~1~AR signaling. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.