Placenta
Volume 31, Issue 10 , Pages 893-901, October 2010

Changes in the Metabolic Footprint of Placental Explant-Conditioned Medium Cultured in Different Oxygen Tensions from Placentas of Small for Gestational Age and Normal Pregnancies

  • R.P. Horgan

      Affiliations

    • The Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland
    • Corresponding Author InformationCorresponding author. Tel.: +353 21 4205023; fax: +353 21 4205025.
    • ,
  • D.I. Broadhurst

      Affiliations

    • The Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland
    • ,
  • W.B. Dunn

      Affiliations

    • The Manchester Centre for Integrative Systems Biology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK
    • School of Chemistry, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK
    • Centre for Advanced Discovery and Experimental Therapeutics, Manchester Biomedical Research Centre, University of Manchester, Manchester, UK
    • ,
  • M. Brown

      Affiliations

    • The Manchester Biomedical Research Centre, Manchester Royal Infirmary and University of Manchester, UK
    • ,
  • A.E.P. Heazell

      Affiliations

    • The Maternal and Fetal Health Research Centre, The University of Manchester, St Mary’s Hospital, Whitworth Park, Manchester M13 0JH, UK
    • ,
  • D.B. Kell

      Affiliations

    • The Manchester Centre for Integrative Systems Biology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK
    • School of Chemistry, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK
    • ,
  • P.N. Baker

      Affiliations

    • Faculty of Medicine & Dentistry, University of Alberta, 2J2.01 WMC, 8440 – 112 Street, Edmonton, AB T6G 2R7 Canada
    • ,
  • L.C. Kenny

      Affiliations

    • The Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Cork, Ireland

Accepted 8 July 2010. published online 16 August 2010.

Abstract 

Being born small for gestational age (SGA) confers significantly increased risks of perinatal morbidity and mortality. Accumulating evidence suggests that an SGA fetus results from a poorly perfused and abnormally developed placenta. Some of the placental features seen in SGA, such as abnormal cell turnover and impaired nutrient transport, can be reproduced by culture of placental explants in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors absorbed by and released from this tissue in vitro. Previously, metabolic footprinting of the conditioned culture media has identified differences in placental explants cultured under normoxic and hypoxic conditions and between normal pregnancies and those complicated by pre-eclampsia. In this study we aimed to examine the differences in the metabolic footprint of placental villous explants cultured at different oxygen (O2) tensions between women who deliver an SGA baby (n = 9) and those from normal controls (n = 8). Placental villous explants from cases and controls were cultured for 96 h in 1% (hypoxic), 6% (normoxic) and 20% (hyperoxic) O2. Metabolic footprints were analysed by Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap Mass Spectrometry (UPLC-MS). 574 metabolite features showed significant difference between SGA and normal at one or more of the oxygen tensions. SGA explant media cultured under hypoxic conditions was observed, on a univariate level, to exhibit the same metabolic signature as controls cultured under normoxic conditions in 49% of the metabolites of interest, suggesting that SGA tissue is acclimatised to hypoxic conditions in vivo. No such behaviour was observed under hyperoxic culture conditions. Glycerophospholipid and tryptophan metabolism were highlighted as areas of particular interest.

Keywords: Metabolomics, Metabolic footprint, Placental villous explants, Oxygen tension, Small for gestational age, Systems biology

 

PII: S0143-4004(10)00262-6

doi:10.1016/j.placenta.2010.07.002

Placenta
Volume 31, Issue 10 , Pages 893-901, October 2010

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