Abstract
This study was designed to identify gene networks in the fetal hypothalamus that are up‐ or down‐regulated in response to a 30 minute period of hypoxia (decreased fetal PaO2 to ~10 mm Hg). Chronically catheterized fetal sheep (130–135 days gestation, term=147d) were euthanized 1 hr after onset of a 30 min hypoxia (n=3) or normoxia (n=3). mRNA was extracted and analyzed using the ovine Agilent 15.5k array, which was annotated in this lab. 241 genes were significantly (p<0.005) upregulated and 880 genes were significantly downregulated. GO terms associated with upregulated genes included ubiquitination, Cu homeostasis, oxidative metabolism. GO terms associated with downregulated genes included cell cycle, immune development, and apoptosis. KEGG analysis indicated a shift from aerobic to anaerobic metabolism and decreased gene expression in hematopoietic cell lineages. None of the regulated genes were controlled by HIF, and were therefore most likely influenced by changes in neurotransmission. We conclude that fetal hypothalamic genomic response to hypoxia reflects appropriate responses in cellular energetics and that it is not likely the result of direct cellular hypoxia.
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