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dc.contributor.authorCindrova-Davies, Terezaen
dc.contributor.authorTissot, van Patot Men
dc.contributor.authorGardner, Len
dc.contributor.authorJauniaux, Een
dc.contributor.authorBurton, Grahamen
dc.contributor.authorCharnock-Jones, Stephenen
dc.date.accessioned2014-12-03T14:38:33Z
dc.date.available2014-12-03T14:38:33Z
dc.date.issued2014-11-11en
dc.identifier.citationCindrova-Davies et al. Molecular Human Reproduction (2014) Vol. 21, Issue 3, pp. 296-308. DOI: 10.1093/molehr/gau105en
dc.identifier.issn1360-9947
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246458
dc.description.abstractEarly human placental and embryonic development occurs in a physiologically low oxygen environment supported by histiotrophic secretions from endometrial glands. In this study, we compare the placental metabolomic profile in the first, second and third trimesters to determine whether the energy demands are adequately met in the first trimester.We investigated whether hypoxia-inducible factors, HIF-1a and/or HIF-2a, might regulate transcription during the first trimester. First and second trimester tissuewas collected using a chorionic villus sampling-like (CVS) technique. Part of each villus sample was frozen immediately and the remainder cultured under 2 or 21%O2+1 mMH2O2, and +the p38 MAPK pathway inhibitor, PD169316. Levels of HIF-1a were assessed by western blotting and VEGFA, PlGF and GLUT3 transcripts were quantified by RT–PCR. Term samples were collected from normal elective Caesarean deliveries. There were no significant differences in concentrations of ADP, NAD+, lactate, and glucose, and in the ATP/ADP ratio, across gestational age. Neither HIF-1a nor HIF-2a could be detected in time-zero CVS samples. However, culture under any condition (2 or 21% O2+1 mM H2O2) increased HIF-1a and HIF-2a. HIF-1a and HIF-2a were additionally detected in specimens retrieved after curettage. HIF-1a stabilization was accompanied by significant increases in VEGFA and GLUT3 and a decrease in PlGF mRNAs. These effects were suppressed by PD169316. In conclusion, our data suggest that first trimester placental tissues are not energetically compromised, and that HIF-1a is unlikely to play an appreciable role in regulating transcriptional activity under steady-state conditions in vivo. However, the pathway may be activated by stress conditions.
dc.description.sponsorshipThis work was supported by the Wellcome Trust (084804/2/08/Z). Funding to pay the Open Access publication charges for this article was provided by theWellcome Trust.
dc.languageEnglishen
dc.language.isoenen
dc.publisherOxford Journals
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectplacentaen
dc.subjectHIF-1aen
dc.subjectfirst trimesteren
dc.subjectmetabolomicsen
dc.subjectenergy statusen
dc.titleEnergy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental developmenten
dc.typeArticle
dc.description.versionThis is the final published version. It originally appeared in Molecular Human Reproduction, at http://dx.doi.org/10.1093/molehr/gau105.en
prism.endingPage308
prism.publicationDate2014en
prism.publicationNameMolecular Human Reproductionen
prism.startingPage296
prism.volume21en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectid084804/2/08/Z
rioxxterms.versionofrecord10.1093/molehr/gau105en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-11-11en
dc.contributor.orcidCindrova-Davies, Tereza [0000-0002-9212-0514]
dc.contributor.orcidBurton, Graham [0000-0001-8677-4143]
dc.contributor.orcidCharnock-Jones, Stephen [0000-0002-2936-4890]
dc.identifier.eissn1460-2407
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (084804/Z/08/Z)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales