Transcriptomics

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2

High oxygen prevents fetal lethality due to lack of catecholamines


ABSTRACT: The catecholamine norepinephrine is required for fetal survival, but its essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase (Th) null] mouse fetuses die at E13.5-E14.5, they resemble wild type fetuses exposed to hypoxia. They exhibit bradycardia (28% reduction in heart rate), thin ventricular myocardium (20% reduction in tissue), epicardial detachment, and death with vascular congestion, hemorrhage and edema. At E12.5, prior to the appearance of morphological deficits associated with Th deletion, catecholamine-deficient fetuses are preferentially killed by experimentally-induced hypoxia and have lower tissue pO2 than wild type siblings. Catecholamine-deficient fetuses also induced HIF-1 target genes to a greater extent than wild type siblings, supporting the notion that null fetuses experience greater hypoxia or have an enhanced response to hypoxia. Hypoxia induces a 13-fold increase in plasma norepinephrine levels, which would be expected to increase heart rate, thereby, improving oxygen delivery in wild type mice. Surprisingly, increasing maternal oxygen (FiO2 33% or 63%) prevents the effects of catecholamine-deficiency, restoring heart rate, myocardial mass and survival of Th null fetuses. We suggest that norepinephrine mediates fetal survival by maintaining oxygen homeostasis as vulnerability to constitutive hypoxia increases as fetal growth accelerates during normal development. Keywords: Comparative with respect to genotype and oxygen conditions The first aim was to compare gene expression of E12.5 mouse fetuses between wild type (Th+/+) versus tyrosine hydroxylase null (Th-/-) animals from normoxic dams. This resulted in 6 arrays. The second aim compared wild type and tyrosine hydroxylase null E12.5 fetuses from dam exposed to hypoxia (8% oxygen) for 6 hours prior to sacrifice at E12.5 of gestation. This resulted in 6 arrays. The third aim was to compare HIF-1 targets behind wt and null fetuses

ORGANISM(S): Mus musculus  

SUBMITTER: Dona Chikaraishi   Rashmi Chandra  Howard Rockman  Alisa Ray  William Wetsel  Margie Ream  Hyung-Gun Kim  Mary Peavey 

PROVIDER: E-GEOD-10341 | ArrayExpress | 2008-06-03

SECONDARY ACCESSION(S): GSE10341PRJNA105581

REPOSITORIES: GEO, ArrayExpress

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High oxygen prevents fetal lethality due to lack of catecholamines.

Ream Margie A MA   Chandra Rashmi R   Peavey Mary M   Ray Alisa M AM   Roffler-Tarlov Suzanne S   Kim Hyung-Gun HG   Wetsel William C WC   Rockman Howard A HA   Chikaraishi Dona M DM  

American journal of physiology. Regulatory, integrative and comparative physiology 20080716 3


The catecholamine norepinephrine is required for fetal survival, but its essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase (Th) null] mouse fetuses die at embryonic day (E)13.5-14.5, they resemble wild-type (wt) fetuses exposed to hypoxia. They exhibit bradycardia (28% reduction in heart rate), thin ventricular myocardium (20% reduction in tissue), epicardial detachment, and death with vascular congestion, hemorrhage, and edema. At E12.5, before the appearance of  ...[more]

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