Effect of Hypoxia on Gene Expression in the Chick Embryonic Heart

Abstract

Our previous results showed that normal embryogenesis involves physiological tissue hypoxia. Hypoxic avian hearts show abnormal myoarchitecture, differences in the extent and distribution of hypoxic regions and increased HIF1α. Here we have used microarray analysis to identify genes differentially expressed between normoxic and hypoxic conditionsChicken eggs were incubated at 38°C under normoxic (21% O2) conditions for the first 48 h and subsequently under hypoxic (16% O2) conditions for 24 h (acute hypoxia) or 144 h (chronic hypoxia). Total RNA was extracted from control and hypoxic chick embryonic hearts, converted into biotin‐labeled material, and then hybridized to Affymetrix Chicken Genome Arrays according to manufacturer's protocols. Transcripts differentially expressed in the short term and long term hypoxic states were identified by the criteria fold change >1.5 and p <0.05 (Student's t‐test). 79 transcripts were significantly up‐regulated and 75 down‐regulated in the hypoxic samples. Functional categorization of these genes detected significant enrichment of biological processes such as cell growth, differentiation, muscle contraction and signal transduction. Additionally, we performed a focused examination of genes previously linked to hypoxia adaption, identifying 10 transcripts that were significantly affected in our hypoxic samples (p<0.05). Given that important hypoxia‐regulated genes (e.g., HIF1α) are known to be regulated at the protein, rather than the mRNA level, our results add significant insight into the transcriptional response that occurs in response to hypoxia.Supported by PRVOUK P35/LF1/5 and P302/11/1308.