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Review: The effects of oxygen on normal and pre-eclamptic placental tissue - insights from metabolomics.
MedLine Citation:
PMID:  21195475     Owner:  NLM     Status:  Publisher    
Placental dysfunction is central to many complications of human pregnancy including pre-eclampsia (PE), intra-uterine growth restriction (IUGR) and stillbirth. The precise molecular pathophysiology of placental dysfunction in these conditions is not known, although oxidative and nitrative stresses have been implicated. Metabolites are low molecular weight chemicals which play an important role in biological function, primarily through metabolism and regulation of biological processes. The holistic study of metabolites, defined as metabolomics or metabolic profiling, has the objective to detect and identify all, or a large complement of all metabolites. Metabolomics is applied to discover new knowledge regarding biological processes and systems. We hypothesised that a metabolomic strategy could (1) provide a reproducible technique to investigate the intracellular metabolism of placental tissue and also metabolites consumed from or secreted in to the extracellular 'metabolic footprint' of in vitro culture systems (2) identify metabolic related differences in placental tissue culture systems subjected to perturbations in oxygen tension and from pregnancies complicated by PE. We review our early studies which demonstrate that a reproducible experimental protocol is required, including the preparation of culture medium and the site of the placenta applied for sampling tissue. We have detected changes in the intracellular metabolome and metabolic footprint of placental tissue in response to altered oxygen tension and PE. We have demonstrated that placental tissue from uncomplicated pregnancies cultured in 1% oxygen (hypoxia) had metabolic similarities to explants from PE pregnancies cultured at 6% oxygen (normoxia). Metabolites requiring further study include lipids, glutamate and glutamine and metabolites related to tryptophan, leukotriene and prostaglandin metabolism. Metabolomics has the potential to identify changes in clinical conditions, such as PE, that are associated with placental molecular pathophysiology.
A E P Heazell; M Brown; S A Worton; W B Dunn
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-30
Journal Detail:
Title:  Placenta     Volume:  -     ISSN:  1532-3102     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006349     Medline TA:  Placenta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Maternal and Fetal Health Research Centre, University of Manchester, Manchester Academic Health Sciences Centre, Manchester M13 9WL, UK.
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