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dc.contributor.authorCindrova-Davies, Terezaen
dc.contributor.authorJones, Carolyn Pen
dc.contributor.authorFogarty, Norah MEen
dc.contributor.authorKingdom, Johnen
dc.contributor.authorBurton, Grahamen
dc.date.accessioned2018-03-15T15:56:26Z
dc.date.available2018-03-15T15:56:26Z
dc.date.issued2017-09en
dc.identifier.issn0143-4004
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274017
dc.description.abstractObjectives: Senescence is a critical feature of mammalian cells, and can be induced by oxidative stress. Evidence exists that placental oxidative stress is a key intermediary in the pathology of pre-eclampsia. The aim was to examine senescence markers in normal placentas across gestation, and in pathological and post-mature pregnancies. Inducers of oxidative stress were used to mimic senescence changes in term explants. Methods: All samples were collected with local ethics approval. First and second trimester samples were from surgical terminations. Term and pre-term controls, and early-onset pre-eclampsia (PE+IUGR) placentas were from caesarean deliveries. Archival paraffin and EM blocks of post-mature placentas (7-21 d post-term) were from the University of Manchester. Term explants were subjected to cyclical hypoxia-reoxygenation (HR) or H2O2 (0-1 M) for 24-48 h to induce oxidative stress. Results: p21 was increased significantly in term homogenates compared to first and second trimester samples, while p16 increased in the second trimester but showed no further difference. p21 was significantly higher in both preterm controls and PE+IUGR compared to term controls. There were no significant differences in p16 among the three groups. Immunostaining revealed nuclear localisation of p21 and phosphorylated histone, γH2AX, in the syncytiotrophoblast, with abundant foci in pathological and post-mature placentas. Abnormal nuclear appearances were also observed in post-mature placentas. In addition, an increased percentage of nuclei were positive for 8-hydroxy-2’-deoxy-guanosine, a marker of oxidised DNA, in pathological placentas compared to age-matched controls. These changes could be mimicked in vitro by challenge with HR or H2O2. Conclusions: Markers of senescence increase in normal placentas with gestational age, and in pathological (PE+IUGR) and post-mature placentas. Oxidative stress triggers these changes in placental explants, and may be the precipitating insult in vivo. The consequent pro-inflammatory secretory phenotype may contribute to the pathophysiology of pre-eclampsia.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleEVIDENCE OF OXIDATIVE STRESS-INDUCED AND GESTATIONAL AGE DEPENDENT SENESCENCE IN PATHOLOGICAL AND POST-MATURE HUMAN PLACENTASen
dc.typeConference Object
prism.endingPage283
prism.publicationDate2017en
prism.publicationNamePLACENTAen
prism.startingPage282
prism.volume57en
dc.identifier.doi10.17863/CAM.21094
dcterms.dateAccepted2017-06-15en
rioxxterms.versionofrecord10.1016/j.placenta.2017.07.190en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-09en
dc.contributor.orcidCindrova-Davies, Tereza [0000-0002-9212-0514]
dc.contributor.orcidBurton, Graham [0000-0001-8677-4143]
dc.identifier.eissn1532-3102
rioxxterms.typeConference Paper/Proceeding/Abstracten
pubs.funder-project-idAnatomical Society (AS) (unknown)
pubs.funder-project-idWellcome Trust (084804/Z/08/Z)
rioxxterms.freetoread.startdate2018-08-30


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