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.

Hdl Handle:
http://hdl.handle.net/10147/206254
Title:
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.
Authors:
Horgan, R P; Broadhurst, D I; Dunn, W B; Brown, M; Heazell, A E P; Kell, D B; Baker, P N; Kenny, L C
Affiliation:
Department of Obstetrics and Gynaecology, University College Cork, Cork, University Maternity Hospital, The Anu Research Centre, Cork, Ireland., richard.horgan@ucc.ie
Citation:
Placenta. 2010 Oct;31(10):893-901. Epub 2010 Aug 13.
Journal:
Placenta
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/206254
DOI:
10.1016/j.placenta.2010.07.002
PubMed ID:
20708797
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 (O(2)) 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) O(2). 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.
Language:
eng
MeSH:
Anoxia/*metabolism; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age/*metabolism; Metabolomics/methods; Oxygen/administration & dosage/*metabolism; Placenta/*metabolism; Pregnancy; Principal Component Analysis; Spectrometry, Mass, Electrospray Ionization; Tissue Culture Techniques
ISSN:
1532-3102 (Electronic); 0143-4004 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHorgan, R Pen_GB
dc.contributor.authorBroadhurst, D Ien_GB
dc.contributor.authorDunn, W Ben_GB
dc.contributor.authorBrown, Men_GB
dc.contributor.authorHeazell, A E Pen_GB
dc.contributor.authorKell, D Ben_GB
dc.contributor.authorBaker, P Nen_GB
dc.contributor.authorKenny, L Cen_GB
dc.date.accessioned2012-01-31T16:43:50Z-
dc.date.available2012-01-31T16:43:50Z-
dc.date.issued2012-01-31T16:43:50Z-
dc.identifier.citationPlacenta. 2010 Oct;31(10):893-901. Epub 2010 Aug 13.en_GB
dc.identifier.issn1532-3102 (Electronic)en_GB
dc.identifier.issn0143-4004 (Linking)en_GB
dc.identifier.pmid20708797en_GB
dc.identifier.doi10.1016/j.placenta.2010.07.002en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206254-
dc.description.abstractBeing 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 (O(2)) 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) O(2). 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAnoxia/*metabolismen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInfant, Newbornen_GB
dc.subject.meshInfant, Small for Gestational Age/*metabolismen_GB
dc.subject.meshMetabolomics/methodsen_GB
dc.subject.meshOxygen/administration & dosage/*metabolismen_GB
dc.subject.meshPlacenta/*metabolismen_GB
dc.subject.meshPregnancyen_GB
dc.subject.meshPrincipal Component Analysisen_GB
dc.subject.meshSpectrometry, Mass, Electrospray Ionizationen_GB
dc.subject.meshTissue Culture Techniquesen_GB
dc.titleChanges in the metabolic footprint of placental explant-conditioned medium cultured in different oxygen tensions from placentas of small for gestational age and normal pregnancies.en_GB
dc.contributor.departmentDepartment of Obstetrics and Gynaecology, University College Cork, Cork, University Maternity Hospital, The Anu Research Centre, Cork, Ireland., richard.horgan@ucc.ieen_GB
dc.identifier.journalPlacentaen_GB
dc.description.provinceMunster-

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