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dc.contributor.authorAye, Irving LMH
dc.contributor.authorGong, Sungsam
dc.contributor.authorAvellino, Giulia
dc.contributor.authorBarbagallo, Roberta
dc.contributor.authorGaccioli, Francesca
dc.contributor.authorJenkins, Benjamin J
dc.contributor.authorKoulman, Albert
dc.contributor.authorMurray, Andrew J
dc.contributor.authorStephen Charnock-Jones, D
dc.contributor.authorSmith, Gordon CS
dc.date.accessioned2022-06-15T15:01:26Z
dc.date.available2022-06-15T15:01:26Z
dc.date.issued2022-06-15
dc.date.submitted2021-11-03
dc.identifier.others42003-022-03530-6
dc.identifier.other3530
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338126
dc.descriptionFunder: Centre for Trophoblast Research, University of Cambridge
dc.description.abstractAbstract: Placental function and dysfunction differ by sex but the mechanisms are unknown. Here we show that sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding spermine synthase (SMS). Female placental trophoblasts demonstrate biallelic SMS expression, associated with increased SMS mRNA and enzyme activity. Polyamine depletion in primary trophoblasts reduced glycolysis and oxidative phosphorylation resulting in decreased acetyl-coA availability and global histone hypoacetylation in a sex-dependent manner. Chromatin-immunoprecipitation sequencing and RNA-sequencing identifies progesterone biosynthesis as a target of polyamine regulated gene expression, and polyamine depletion reduced progesterone release in male trophoblasts. The effects of polyamine depletion can be attributed to spermine as SMS-silencing recapitulated the effects on energy metabolism, histone acetylation, and progesterone release. In summary, spermine metabolism alters trophoblast gene expression through acetyl-coA biosynthesis and histone acetylation, and SMS escape from X inactivation explains some features of human placental sex differences.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/443/494
dc.subject/631/443/494/2732
dc.subject/13/106
dc.subject/38
dc.subject/38/91
dc.subject/9
dc.subject/82
dc.subject/82/58
dc.subjectarticle
dc.titlePlacental sex-dependent spermine synthesis regulates trophoblast gene expression through acetyl-coA metabolism and histone acetylation
dc.typeArticle
dc.date.updated2022-06-15T15:01:25Z
prism.issueIdentifier1
prism.publicationNameCommunications Biology
prism.volume5
dc.identifier.doi10.17863/CAM.85535
dcterms.dateAccepted2022-05-24
rioxxterms.versionofrecord10.1038/s42003-022-03530-6
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidKoulman, Albert [0000-0001-9998-051X]
dc.identifier.eissn2399-3642


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