A1 adenosine receptors play an essential role in protecting the embryo against hypoxia
- 5 June 2007
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (23), 9697-9702
- https://doi.org/10.1073/pnas.0703557104
Abstract
Embryos can be exposed to environmental factors that induce hypoxia. Currently, our understanding of the effects of hypoxia on early mammalian development is modest. Potential mediators of hypoxia action include the nucleoside adenosine, which acts through A(1) adenosine receptors (A(1)ARs) and mediates adverse effects of hypoxia on the neonatal brain. We hypothesized that A(1)ARs may also play a role in mediating effects of hypoxia on the embryo. When pregnant dams were exposed to hypoxia (10% O(2)) beginning at embryonic day (E) 7.5 or 8.5 and continued for 24-96 h, A(1)AR+/+ embryos manifested growth inhibition and a disproportionate reduction in heart size, including thinner ventricular walls. Yet, when dams were exposed to hypoxia, embryos lacking A(1)ARs (A(1)AR-/-) had much more severe growth retardation than A(1)AR+/+ or +/- embryos. When levels of hypoxia-inducible factor 1alpha (HIF1alpha) were examined, A(1)AR-/- embryos had less stabilized HIF1alpha protein than A(1)AR+/- littermates. Normal patterns of cardiac gene expression were also disturbed in A(1)AR-/- embryos exposed to hypoxia. These results show that short periods of hypoxia during early embryogenesis can result in intrauterine growth retardation. We identify adenosine and A(1)ARs as playing an essential role in protecting the embryo from hypoxia.Keywords
This publication has 45 references indexed in Scilit:
- Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: Role of the BMP-4 geneProceedings of the National Academy of Sciences of the United States of America, 2006
- Mitochondrial regulation of hypoxia-induced increase of adrenomedullin mRNA in HL-1 cellsBiochemical and Biophysical Research Communications, 2006
- Oxygenation Inhibits the Physiological Tissue-Protecting Mechanism and Thereby Exacerbates Acute Inflammatory Lung InjuryPLoS Biology, 2005
- Role of myocardial hypoxia in the remodeling of the embryonic avian cardiac outflow tractDevelopmental Biology, 2004
- Increased Fibronectin Deposition in Embryonic Hearts of Retinol-Binding Protein–Null MiceCirculation Research, 2003
- Rho‐associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferationDevelopmental Dynamics, 2002
- Hypoxia in Vivo Decreases Peroxisome Proliferator-Activated Receptor α-Regulated Gene Expression in Rat HeartBiochemical and Biophysical Research Communications, 2001
- Hypoxia Regulates the Expression of the Adrenomedullin and HIF-1 Genes in Cultured HL-1 CardiomyocytesBiochemical and Biophysical Research Communications, 1999
- The ontogeny of cardiac and neural A1 adenosine receptor expression in ratsDevelopmental Brain Research, 1995
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970