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dc.contributor.authorGong, Sungsam
dc.contributor.authorSovio, Ulla
dc.contributor.authorAye, Irving Lmh
dc.contributor.authorGaccioli, Francesca
dc.contributor.authorDopierala, Justyna
dc.contributor.authorJohnson, Michelle D
dc.contributor.authorWood, Angela M
dc.contributor.authorCook, Emma
dc.contributor.authorJenkins, Benjamin J
dc.contributor.authorKoulman, Albert
dc.contributor.authorCasero, Robert A
dc.contributor.authorConstância, Miguel
dc.contributor.authorCharnock-Jones, D Stephen
dc.contributor.authorSmith, Gordon Cs
dc.date.accessioned2018-09-20T12:03:54Z
dc.date.available2018-09-20T12:03:54Z
dc.date.issued2018-07-12
dc.identifier.issn2379-3708
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280456
dc.description.abstractPreeclampsia and fetal growth restriction (FGR) are major causes of the more than 5 million perinatal and infant deaths occurring globally each year, and both are associated with placental dysfunction. The risk of perinatal and infant death is greater in males, but the mechanisms are unclear. We studied data and biological samples from the Pregnancy Outcome Prediction (POP) study, a prospective cohort study that followed 4,212 women having first pregnancies from their dating ultrasound scan through delivery. We tested the hypothesis that fetal sex would be associated with altered placental function using multiomic and targeted analyses. We found that spermine synthase (SMS) escapes X-chromosome inactivation (XCI) in the placenta and is expressed at lower levels in male primary trophoblast cells, and male cells were more sensitive to polyamine depletion. The spermine metabolite N1,N12-diacetylspermine (DiAcSpm) was higher in the female placenta and in the serum of women pregnant with a female fetus. Higher maternal serum levels of DiAcSpm increased the risk of preeclampsia but decreased the risk of FGR. To our knowledge, DiAcSpm is the first maternal biomarker to demonstrate opposite associations with preeclampsia and FGR, and this is the first evidence to implicate polyamine metabolism in sex-related differences in placentally related complications of human pregnancy.
dc.description.sponsorshipThe work was supported by NIHR Cambridge Comprehensive Biomedical Research Centre and the Medical Research Council (United Kingdom; G1100221 to GCSS and DSC-J and MRC_MC_UU_12012/4 to MC).
dc.format.mediumElectronic
dc.languageeng
dc.publisherAmerican Society for Clinical Investigation
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectExpression profiling
dc.subjectObstetrics/gynecology
dc.subjectPolyamines
dc.subjectReproductive Biology
dc.subjectCell Survival
dc.subjectFemale
dc.subjectFetal Development
dc.subjectFetal Growth Retardation
dc.subjectGene Expression Regulation
dc.subjectGenes, X-Linked
dc.subjectGestational Age
dc.subjectHumans
dc.subjectMale
dc.subjectPlacenta
dc.subjectPolyamines
dc.subjectPre-Eclampsia
dc.subjectPregnancy
dc.subjectPregnancy Complications
dc.subjectProspective Studies
dc.subjectRisk Assessment
dc.subjectSequence Analysis, RNA
dc.subjectSex Factors
dc.subjectSpermine
dc.subjectSpermine Synthase
dc.subjectTranscriptome
dc.subjectTrophoblasts
dc.subjectUltrasonography, Prenatal
dc.subjectUnited Kingdom
dc.titlePlacental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia.
dc.typeArticle
prism.issueIdentifier13
prism.publicationDate2018
prism.publicationNameJCI Insight
prism.volume3
dc.identifier.doi10.17863/CAM.27827
dcterms.dateAccepted2018-05-31
rioxxterms.versionofrecord10.1172/jci.insight.120723
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-07-12
dc.contributor.orcidGong, Sung [0000-0001-5796-4423]
dc.contributor.orcidSovio, Ulla [0000-0002-0799-1105]
dc.contributor.orcidAye, Irving [0000-0003-3400-5005]
dc.contributor.orcidGaccioli, Francesca [0000-0001-7178-8921]
dc.contributor.orcidWood, Angela [0000-0002-7937-304X]
dc.contributor.orcidKoulman, Albert [0000-0001-9998-051X]
dc.contributor.orcidCharnock-Jones, Stephen [0000-0002-2936-4890]
dc.contributor.orcidSmith, Gordon [0000-0003-2124-0997]
dc.identifier.eissn2379-3708
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (G1100221)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (3819-1718-09)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/I014594/1)
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idMedical Research Council (MC_UU_12012/4)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MR/K021133/1)
pubs.funder-project-idMRC (MC_UU_00014/4)
cam.issuedOnline2018-07-12


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International