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. (c) 2008 Wiley-Liss, Inc.
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. (c) 2008 Wiley-Liss, Inc.
Authors: Antoon F M Moorman; Alexandre T Soufan; Jaco Hagoort; Piet A J de Boer; Vincent M Christoffels Journal: Ann N Y Acad Sci Date: 2004-05 Impact factor: 5.691
Authors: Margaret L Kirby; Aaron Lawson; Harriett A Stadt; Donna H Kumiski; Kathleen T Wallis; Eileen McCraney; Karen L Waldo; Yin-Xiong Li; Gary C Schoenwolf Journal: Dev Biol Date: 2003-01-15 Impact factor: 3.582
Authors: Eduardo Villamor; Carolina G A Kessels; Karin Ruijtenbeek; Robert J van Suylen; Jaques Belik; Jo G R de Mey; Carlos E Blanco Journal: Am J Physiol Regul Integr Comp Physiol Date: 2004-04-29 Impact factor: 3.619
Authors: Shi Gu; Michael W Jenkins; Lindsy M Peterson; Yong-Qiu Doughman; Andrew M Rollins; Michiko Watanabe Journal: Dev Dyn Date: 2012-01-23 Impact factor: 3.780
Authors: Christopher C Wendler; Ryan R Poulsen; Satish Ghatpande; Robert W Greene; Scott A Rivkees Journal: BMC Dev Biol Date: 2010-05-28 Impact factor: 1.978