Analysis of the metabolic footprint and tissue metabolome of placental villous explants cultured at different oxygen tensions reveals novel redox biomarkers

被引：44

作者：

Heazell, A. E. P. ^{[1
]}

Brown, M. ^{[2
]}

Dunn, W. B. ^{[3
]}

Worton, S. A. ^{[1
]}

Crocker, I. P. ^{[1
]}

Baker, P. N. ^{[1
]}

Kell, D. B. ^{[2
,3
]}

机构：

[1] Univ Manchester, St Marys Hosp, Maternal & Fetal Hlth Res Grp, Manchester M13 0JH, Lancs, England

[2] Univ Manchester, Manchester Interdisciplinary Biocentre, Bioanalyt Sci Grp, Manchester M1 7DN, Lancs, England

[3] Univ Manchester, Manchester Interdisciplinary Biocentre, Sch Chem, Manchester Ctr Integrat Syst Biol, Manchester M1 7DN, Lancs, England

来源：

PLACENTA | 2008年 / 29卷 / 08期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国工程与自然科学研究理事会;

关键词：

placental villous explants; oxygen; metabolomics; 2-deoxyribose; metabolic footprinting;

D O I：

10.1016/j.placenta.2008.05.002

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pre-eclampsia (PE) is a multi-system disorder of pregnancy hypothesised to arise from circulating factors derived from an unhealthy placenta. Some changes in placental phenotype seen in PE can be reproduced by Culture in altered oxygen (0,) tension. Currently, these circulating factors are unidentitied. partly due to the complexity of maternal plasma. Investigation of factors released front placental tissue provides a potential method to identify bioactive compounds. Experimental strategies to Study compounds present in a biological system have expanded greatly in recent years. Metabolomics can detect and identify endogenous and secreted metabolites. We aimed to determine whether metabolites Could lie identified in placental Cultures with acceptable experimental variability and to determine whether altered O-2 tension affects the composition of the placental metabolome. In this study we used gas-chromatography-mass spectroscopy to determine the presence of metabolites in conditioned Culture medium (CCM) and tissue lysates of placental villous explants cultured in 1, 6 and 20% atmospheric 0, for 96 It. This experimental strategy had an intra-assay variation of 6.1-11.6%. Intra and inter-placental variability were 15.7-35.8% and 44.8-46.2% respectively. Metabolic differences were identified between samples cultured in 1.6 and 20% 0, in both CCM and tissue lysate. Differentially expressed metabolites included: 2-deoxyribose, threitol or erythritol and hexadecanoic acid. We conclude that metabolomic strategies offer I novel approach to investigate placental function. When conducted under carefully controlled conditions, with appropriate statistical analysis, metabolic differences can be identified in placental explants in response to altered O-2 tension. Metabolomics could be used to identify changes in conditions associated with placental pathology. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：691 / 698

页数：8

共 45 条

[1] High-throughput classification of yeast mutants for functional genomics using metabolic footprinting [J].