Project description:The late-gestation fetal sheep responds to hypoxia with physiological, neuroendocrine, and cellular responses that aid in fetal survival . The response of the fetus to hypoxia represents a coordinated effort to maximize oxygen transfer from the mother and minimize wasteful oxygen consumption by the fetus. While there have been many studies aimed at investigating the coordinated physiological and endocrine responses to hypoxia, and while immunohistochemical or in situ hybridization studies have revealed pathways supporting the endocrine function of the pituitary, there is little known about the coordinated cellular response of the pituitary to the hypoxia. The objective of this study was to use transcriptomics and systems analysis to determine significantly altered biological processes in the late gestation ovine fetal pituitary one hour after a 30 minute period of hypoxia, produced by lowering the inspired oxygen content in the maternal inspired gas. We found that the acute response to 30 min of transient hypoxia in the late-gestation fetus results in reduced cellular metabolism and a pattern of gene expression that is consistent with cellular oxygen and ATP starvation. The response is not consistent with gene regulation by HIF1A .
Project description:Fetuses respond to transient hypoxia (a common stressor in utero) with cellular responses that are appropriate for promoting survival of the fetus. The present experiment was performed to identify the acute genomic responses of the fetal hypothalamus to transient hypoxia. Three fetal sheep were exposed to 30 min of hypoxia and hypothalamic mRNA extracted from samples collected 30 min after return to normoxia. These samples were compared to those from 4 normoxic control fetuses using the Agilent 019921 ovine array. Differentially-regulated genes were analyzed by network analysis and by gene ontology analysis, identifying statistically significant overrepresentation of biological processes. Real-time PCR of selected genes supported the validity of the array data. Hypoxia induced increased expression of genes involved in response to oxygen stimulus, RNA splicing, anti-apoptosis, vascular smooth muscle proliferation, and positive regulation of Notch receptor target. Downregulated genes were involved in metabolism, antigen receptor-mediated immunity, macromolecular complex assembly, S-phase, translation elongation, RNA splicing, protein transport, and post-transcriptional regulation. We conclude that these results emphasize that the cellular response to hypoxia involves reduced metabolism, the involvement of the fetal immune system, and the importance of glucocorticoid signaling. 3 Ventilatory Hypoxia (VH) and 4 Control (con) fetuses. All fetuses were chronically catheterized and in late gestation. Hypoxia produced by low PO2 in maternal inspired gas for 30 min, followed by normoxia recovery for 30 min. Control fetuses maintained at normoxia for 30 min, followed by another 30 min of normoxia. Hypothalami collected for mRNA at end of normoxic recovery period.
Project description:Fetuses respond to transient hypoxia (a common stressor in utero) with cellular responses that are appropriate for promoting survival of the fetus. The present experiment was performed to identify the acute genomic responses of the fetal hypothalamus to transient hypoxia. Three fetal sheep were exposed to 30 min of hypoxia and hypothalamic mRNA extracted from samples collected 30 min after return to normoxia. These samples were compared to those from 4 normoxic control fetuses using the Agilent 019921 ovine array. Differentially-regulated genes were analyzed by network analysis and by gene ontology analysis, identifying statistically significant overrepresentation of biological processes. Real-time PCR of selected genes supported the validity of the array data. Hypoxia induced increased expression of genes involved in response to oxygen stimulus, RNA splicing, anti-apoptosis, vascular smooth muscle proliferation, and positive regulation of Notch receptor target. Downregulated genes were involved in metabolism, antigen receptor-mediated immunity, macromolecular complex assembly, S-phase, translation elongation, RNA splicing, protein transport, and post-transcriptional regulation. We conclude that these results emphasize that the cellular response to hypoxia involves reduced metabolism, the involvement of the fetal immune system, and the importance of glucocorticoid signaling.