Fetal hypoxia results in sex- and cell type-specific alterations in postnatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE216946 | GEO | 2023/03/22
REPOSITORIES: GEO
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Project description:Microarray of whole blood maternal samples comparing the expression of genes in the maternal blood in pregnancies where the fetus was hypoxic at birth compared to those where the fetus was normoxic at birth. Intrapartum hypoxia is associated with severe neonatal morbidity and mortality. Current techniques to assess fetal hypoxic status during labour have a poor sensitivity. At birth, the lactate level in umbilical cord blood is used to assess the degree of fetal hypoxia during birth, such that a high lactate reflects a hypoxic fetus and a low lactate a normoxic fetus. We collected maternal blood prior to delivery and compared the expression of genes in the maternal blood in women delivering a normoxic or hypoxic fetus as evidenced by umbilcal cord blood levels.
2014-05-08 | E-MTAB-2054 | biostudies-arrayexpress
Project description:Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage and is a common cause of neurological handicaps in adulthood. To elucidate the molecular events occurring in cerebral cortices of mature rats (8 weeks old) after neonatal HI brain insult, we performed comprehensive gene expression and gene network analyses using a DNA microarray system (Agilent 4x44K). A rat model of neonatal HI encephalopathy (Rice model) was obtained by unilateral ligation of the common carotid artery of 7-day-old rats with hypoxia (exposure to 8% oxygen). Due to the HI insult-related breakdown of the ipsilateral hemisphere in the brain, RNAs were prepared from the contralateral cerebral cortices of 8-week-old rats and analyzed by DNA microarray. Biofunctional analysis of differentially regulated genes revealed that many upregulated genes were related to cell death signaling, such as the arachidonic acid cascade. In contrast, many downregulated genes were related to gene expression, reflecting progressive damage by the HI insult, even within the contralateral cerebral hemisphere. Seven-day-old Wistar rats were assigned to two groups: the control group and the Rice group (four pups in each group). HI brain insult was not induced in the control group rats. The Rice group rats were subjected to a modified LevineM-bM-^@M-^Ys procedure to induce HI brain injury. The Rice group rats were anesthetized with ether, and the left carotid artery was sectioned between double ligatures with 4-0 surgical silk. The rats were allowed to recover for 1M-bM-^@M-^S2 h and then exposed to 1 h of hypoxia in a plastic chamber that was perfused with a mixture of humidified 8% oxygen balanced with nitrogen. The temperature inside the chamber was maintained at 33 M-BM-0C, the usual temperature generated when pups huddle with the mother. The cerebral cortexes contralateral to the HI brain insult and those of the same side of the control animals were used for the experiment.
2012-06-27 | E-GEOD-37777 | biostudies-arrayexpress
Project description:Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage and is a common cause of neurological handicaps in adulthood. To elucidate the molecular events occurring in cerebral cortices of mature rats (8 weeks old) after neonatal HI brain insult, we performed comprehensive gene expression and gene network analyses using a DNA microarray system (Agilent 4x44K). A rat model of neonatal HI encephalopathy (Rice model) was obtained by unilateral ligation of the common carotid artery of 7-day-old rats with hypoxia (exposure to 8% oxygen). Due to the HI insult-related breakdown of the ipsilateral hemisphere in the brain, RNAs were prepared from the contralateral cerebral cortices of 8-week-old rats and analyzed by DNA microarray. Biofunctional analysis of differentially regulated genes revealed that many upregulated genes were related to cell death signaling, such as the arachidonic acid cascade. In contrast, many downregulated genes were related to gene expression, reflecting progressive damage by the HI insult, even within the contralateral cerebral hemisphere.
2012-06-28 | GSE37777 | GEO
Project description:Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.
2017-08-22 | GSE86346 | GEO
Project description:Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.
2017-08-22 | GSE86408 | GEO
Project description:The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. However, little is known about the biochemical and molecular response of the fetal brain to transient hypoxia. The present study was designed to use transcriptomics and systems biology modeling to identify major biological responses of the fetal hypothalamus to transient hypoxia. We also investigated the effect of ketamine, an FDA approved anesthetic that has anti-inflammatory properties in various tissues. Chronically catheterized fetal sheep (122±5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2 ~50 %) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. Messenger RNA was isolated from fetal hypothalamus collected 24 hours after hypoxia, and was analyzed for gene expression using the Agilent 15.5k ovine microarray. Hypoxia increased expression of 280 and decreased expression of 357 genes. Genes increased by hypoxia were associated with immune responses, consistent with stimulation by lipopolysaccharide. Pretreatment of the fetuses with ketamine reduced immune/inflammation responses. Immunohistochemical analysis revealed that the number of microglia/macrophages in the anterior hypothalamus was increased by hypoxia and that the increase was blunted by ketamine. We conclude that transient hypoxia stimulates an inflammatory/immune response in the fetal hypothalamus and that transcriptomics/systems biology modeling is a useful and valid tool for investigation of biological function in the fetal sheep.
2017-07-31 | GSE82016 | GEO
Project description:Gestational hypoxia presents a significant stress to an unborn fetus that can lead to significant complications related to fetal growth restriction and resulting in diseases in the newborn as well as those manifesting later in life. Recent evidence indicates that inflammation and oxidative stress are contributing factors to hypoxia-related diseases. The Center for Perinatal Biology at Loma Linda University has studied gestational chronic hypoxia in a sheep model for over 20 years to study dysfunction of vascular and nonvascular tissues derived from mothers, fetuses and offspring. In this project we are attempting to use metabolomics to assess metabolic dysregulation in vascular tissues along with markers of oxidative stress and inflammation in the mother and offspring to determine the extent of dysregulation due to chronic hypoxia. Untargeted metabolomics analysis focused on sheep plasma and arteries from the lung, resistance arteries in the brain, uterine arteries, and cultured human myocytes will be used to explore markers of glucose and lipid metabolism disruption. Targeted analyses of oxylipins and endocannabinoids will be used on the same samples to explore markers of oxidative stress and inflammation, which should be increased during hypoxia. This study should delineate pathways and biomarkers that help explain how hypoxia leads to the development of neonatal as well as adult-onset diseases associated with chronic hypoxia that are inter-related with fetal growth restriction.
2017-08-29 | ST000872 | MetabolomicsWorkbench
Project description:Gestational hypoxia presents a significant stress to an unborn fetus that can lead to significant complications related to fetal growth restriction and resulting in diseases in the newborn as well as those manifesting later in life. Recent evidence indicates that inflammation and oxidative stress are contributing factors to hypoxia-related diseases. The Center for Perinatal Biology at Loma Linda University has studied gestational chronic hypoxia in a sheep model for over 20 years to study dysfunction of vascular and nonvascular tissues derived from mothers, fetuses and offspring. In this project we are attempting to use metabolomics to assess metabolic dysregulation in vascular tissues along with markers of oxidative stress and inflammation in the mother and offspring to determine the extent of dysregulation due to chronic hypoxia. Untargeted metabolomics analysis focused on sheep plasma and arteries from the lung, resistance arteries in the brain, uterine arteries, and cultured human myocytes will be used to explore markers of glucose and lipid metabolism disruption. Targeted analyses of oxylipins and endocannabinoids will be used on the same samples to explore markers of oxidative stress and inflammation, which should be increased during hypoxia. This study should delineate pathways and biomarkers that help explain how hypoxia leads to the development of neonatal as well as adult-onset diseases associated with chronic hypoxia that are inter-related with fetal growth restriction.
2017-08-30 | ST000873 | MetabolomicsWorkbench
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 .
2015-10-01 | GSE69246 | GEO
Project description:Acute fetal hypoxia is a form of fetal stress that stimulates renal vasoconstriction and ischemia as a consequence of the physiological redistribution of combined ventricular output. We have demonstrated that hypoxia in late ovine gestation induces inflammation in the brain that is ameliorated by treatment with ketamine. We hypothesized that the fetal kidney would also respond to hypoxia with an increase in the expression of inflammatory genes, and that ketamine (an N-Methyl-D-aspartate receptor antagonist) would reduce or block this response. Enriched biological processes for the 427 upregulated genes were immune and inflammatory responses and for the 946 down-regulated genes were metabolic processes. Ketamine countered the effects of hypoxia on upregulated immune/inflammatory responses as well as the down-regulated metabolic responses. We conclude that our transcriptomics modeling predicts that hypoxia activates inflammatory pathways and reduces metabolism in the fetal kidney cortex, and ketamine blocks or ameliorates this response. The results suggest that ketamine may have therapeutic potential for protection from ischemic renal damage. At the time of surgery, fetuses were randomly assigned to one of the four groups (n=3-4/group): normoxic control, normoxia+ketamine, hypoxic control, and hypoxia+ketamine. Hypoxia was induced for 30 min in chronically catheterized fetal sheep (125±3 d; term=145-147d), with or without ketamine (3 mg/kg) administered intravenously to the fetus 10 min prior to hypoxia. Fetuses were euthanized 24 hours after the onset of hypoxia, and the kidney cortex were collected for RNA extraction and gene array studies. Gene expression was analyzed using ovine Agilent 15.5 k array and validated with qPCR. Significant differences in gene expression between groups were determined with t-statistics using the limma package for R (Pâ¤0.05).
2016-09-01 | E-GEOD-66920 | biostudies-arrayexpress