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Decidualisation and placentation defects are a major cause of age-related reproductive decline.

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cam.issuedOnline2017-09-05
dc.contributor.authorWoods, Laura
dc.contributor.authorPerez-Garcia, Vicente
dc.contributor.authorKieckbusch, Jens
dc.contributor.authorWang, Xiaoqiu
dc.contributor.authorDeMayo, Francesco
dc.contributor.authorColucci, Francesco
dc.contributor.authorHemberger, Myriam
dc.contributor.orcidWoods, Laura [0000-0003-4752-025X]
dc.contributor.orcidPerez-Garcia, Vicente [0000-0001-5594-1607]
dc.contributor.orcidHemberger, Myriam [0000-0003-3332-6958]
dc.date.accessioned2018-12-18T00:31:11Z
dc.date.available2018-12-18T00:31:11Z
dc.date.issued2017-09-05
dc.description.abstractMammalian reproductive performance declines rapidly with advanced maternal age. This effect is largely attributed to the exponential increase in chromosome segregation errors in the oocyte with age. Yet many pregnancy complications and birth defects that become more frequent in older mothers, in both humans and mice, occur in the absence of karyotypic abnormalities. Here, we report that abnormal embryonic development in aged female mice is associated with severe placentation defects, which result from major deficits in the decidualisation response of the uterine stroma. This problem is rooted in a blunted hormonal responsiveness of the ageing uterus. Importantly, a young uterine environment can restore normal placental as well as embryonic development. Our data highlight the pivotal, albeit under-appreciated, impact of maternal age on uterine adaptability to pregnancy as major contributor to the decline in reproductive success in older females.Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.
dc.description.sponsorshipThis work was supported by the Biotechnology and Biological Sciences Research Council (Strategic Programme Grant BB/J004499/1) and by the Centre for Trophoblast Research, University of Cambridge, UK. L.W. is supported by a Medical Research Council DTP studentship and J.K. is the recipient of a Next-Generation Fellowship awarded by the Centre for Trophoblast Research, University of Cambridge, UK.
dc.format.mediumElectronic
dc.identifier.doi10.17863/CAM.34358
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287048
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41467-017-00308-x
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAge Factors
dc.subjectAging
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectDecidua
dc.subjectEmbryonic Development
dc.subjectFemale
dc.subjectGene Expression Profiling
dc.subjectHumans
dc.subjectMale
dc.subjectMaternal Age
dc.subjectMice, Inbred C57BL
dc.subjectPlacenta
dc.subjectPlacentation
dc.subjectPregnancy
dc.subjectPregnancy Complications
dc.subjectReproduction
dc.subjectUterus
dc.titleDecidualisation and placentation defects are a major cause of age-related reproductive decline.
dc.typeArticle
dcterms.dateAccepted2017-06-20
prism.issueIdentifier1
prism.publicationDate2017
prism.publicationNameNat Commun
prism.startingPage352
prism.volume8
pubs.funder-project-idWellcome Trust (200841/Z/16/Z)
rioxxterms.licenseref.startdate2017-09-05
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-017-00308-x

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