Ectopic Pregnancy as a Model to Identify Endometrial Genes and Signaling Pathways Important in Decidualization and Regulated by Local Trophoblast 英文参考文献.docVIP

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Ectopic Pregnancy as a Model to Identify Endometrial Genes and Signaling Pathways Important in Decidualization and Regulated by Local Trophoblast 英文参考文献.doc

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Ectopic Pregnancy as a Model to Identify Endometrial Genes and Signaling Pathways Important in Decidualization and Regulated by Local Trophoblast 英文参考文献

EctopicPregnancyasaModeltoIdentifyEndometrial GenesandSignalingPathwaysImportantin DecidualizationandRegulatedbyLocalTrophoblast W.ColinDuncan1.,JulieL.V.Shaw1.,StewartBurgess2,SarahE.McDonald1,HilaryO.D.Critchley1, AndrewW.Horne1* 1MRCCentreforReproductiveHealth,TheUniversityofEdinburgh,Edinburgh,Midlothian,UnitedKingdom,2MoredunResearchInstitute,Penicuik,Midlothian,United Kingdom Abstract The endometrium in early pregnancy undergoes decidualization and functional changes induced by local trophoblast, which are not fully understood. We hypothesized that endometrium from tubal ectopic pregnancy (EP) could be interrogated to identify novel genes and pathways involved in these processes. Gestation-matched endometrium was collectedfromwomenwithEP(n=11)andintrauterinepregnancies(IUP)(n=13).RNAwasextractedfromthetissue.In addition,tissueswerepreparedforhistologicalanalysisfordegreeofdecidualization.Wecompareda)thesamplesfromEP thatweredecidualized(n=6)withnon-decidualizedsamples(n=5),andb)thedecidualizedEP(n=6)withdecidualization- matched IUP (n=6) samples using an Affymetrix gene array platform, with Ingenuity Pathway Analysis, combined with quantitativeRT-PCR.ExpressionofPRLandIGFBP1wasusedtoconfirmthedegreeofdecidualizationineachgroup.There werenodifferencesinPRLorIGFBP1expressioninthedecidualization-matchedsamplesbutamarkedreduction(P,0.001) inthenon-decidualizedsamples.Decidualizationwasassociatedwithincreasedexpressionof428genesincludingSCARA5 (181-fold),DKK1(71-fold)andPROK1(32-fold),anddecreasedexpressionof230genesincludingMMP-7(35-fold)andSFRP4 (21-fold).ThetopcanonicalpathwaysassociatedwiththesedifferentiallyexpressedgeneswereNaturalKillerCellandWnt/ b-Catenin signaling. Local trophoblast was associated with much less alterationof endometrial gene expression with an increase in 56 genes, including CSH1 (8-fold), and a reduction in 29 genes including CRISP3 (8-fold). The top associated canonicalpathwaywasAntigenPresentation.ThestudyofendometriumfromtubalEPmayp