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The perinatal transition of the circulating metabolome in a nonhuman primate.

ABSTRACT: The fetal-to-neonatal transition is one of the most complex processes in biological existence; much is unknown about this transition on the molecular and biochemical level. Based on growing metabolomics literature, we hypothesize that metabolomic analysis will reveal the key biochemical intermediates that change during the birth transition.Using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS), we identified 100 metabolites that changed during this transition. Of these 100 metabolites, 23 demonstrated significant change during the first 72?h. Of note, four intermediates of the tricarboxylic acid (TCA) cycle were identified (?-ketoglutaric acid, fumaric acid, malic acid, and succinyl-CoA), demonstrating a consistent rate of rise during the study. This may signify the transition of the neonate from a hypoxic in utero environment to an oxygen-rich environment. Important signaling molecules were also identified, including myo-inositol and glutamic acid.GC × GC-TOFMS was able to identify important metabolites associated with metabolism and signaling. These data can be used as a baseline for normal birth transition, which may aid in future perinatal research investigations.Late-preterm Macaca nemestrina were delivered by hysterotomy, with plasma drawn from the cord blood and after birth at eight additional time points to 72?h of age.

SUBMITTER: Beckstrom AC

PROVIDER: S-EPMC4813511 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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The perinatal transition of the circulating metabolome in a nonhuman primate.

Beckstrom Andrew C AC Tanya Pattaraporn P Humston Elizabeth M EM Snyder Laura R LR Synovec Robert E RE Juul Sandra E SE

Pediatric research 20120215 4 Pt 1

<h4>Introduction</h4>The fetal-to-neonatal transition is one of the most complex processes in biological existence; much is unknown about this transition on the molecular and biochemical level. Based on growing metabolomics literature, we hypothesize that metabolomic analysis will reveal the key biochemical intermediates that change during the birth transition.<h4>Results</h4>Using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS), we identified 100 ...[more]

PMID: 22391633

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Project description:Little is known about the repertoire of nonhuman primate kidney genes expressed throughout development. The present work establishes an understanding of the primate renal transcriptome at different stages of fetal development and defines the framework of gene expression in the context of renal maturation, which provides a basis for identifying deviations in transcriptome expression resulting from suboptimal conditions during renal development. The baboon kidney transcriptome was characterized at 60 days gestation (DG), 90DG, 125DG, 160DG and adulthood (6-12 years) using human genome arrays to identify differential gene expression in the context of biological pathways and hierarchical clusters. Whole genome expression profiling showed 11,331 genes that were expressed during kidney development, 4,698 of which were differentially expressed among the developmental time points. Pathway analysis indicated activation of annotated pathways previously reported to be important to kidney development and pathways not reported as relevant to kidney development. QRT-PCR for genes central to these pathways validated expression profiles and revealed differences between males and females at specific times in gestation. Hierarchical clustering indicated that two clusters best fit the data, one containing genes that increased in expression from 60DG to adult and one that decreased. Cluster analysis also revealed gene splice variants with discordant expression profiles during development. For example, SMAD4, which is central to Wnt signaling, TGF-β signaling and cell cycle, showed up-regulation of the full-length splice variant during development and down-regulation of a shorter variant that is missing DNA binding and protein heterotrimerization domains suggesting decreased inhibition of cell proliferation, which may impact renal cell number and maturation. This study provides the first detailed genetic analysis of the developing primate kidney, and our findings of discordant expression of gene splice variants suggest that gene arrays likely provide a simplified view and demonstrate the need to study the fetal renal proteome.

Dataset Information

The perinatal transition of the circulating metabolome in a nonhuman primate.

Publications

The perinatal transition of the circulating metabolome in a nonhuman primate.

Similar Datasets

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