AlphaVBeta3 Integrin Expression within Uterine Endometrium in Unexplained Infertility

Abstract

Summary I nfertilityiscustomarilydefinedastheinabilitytoconceiveafter1yearofunwantednon-conceptionwithunprotectedintercourseinthefertilephaseofthemenstrualcycle.ThePracticeCommitteeoftheAmericanSocietyforReproductiveMedicine(ASRM)haspublishedguidelinesforastandardinfertilityevaluation. Unexplainedinfertilityreferstotheabsenceofadefinablecauseforacouple’sfailuretoachievepregnancyafter12monthsofattemptingconceptiondespiteathoroughevaluation.Despiteimproveddiagnostictechniques,theaverageincidenceofunexplainedinfertilityhasbeenreportedtobeapproximately15%.Alargenumberofhumanpregnanciesfailduringtheimplantationstagebecausetheuterineendometriumisunreceptivetotheimplantingembryo. Embryoimplantationrepresentsthemostcriticalstepofthereproductiveprocessinmanyspecies.Successfulimplantationrequiresareceptiveendometrium,anormalandfunctionalembryoattheblastocystdevelopmentalstageandasynchronizeddialoguebetweenmaternalandembryonictissues. Theendometriumisreceptivetoblastocystimplantationduringaspatiallyandtemporallyrestrictedwindow,calledtheimplantationwindow.Inhumans,thisperiodbegins6-10daysaftertheLHsurgeandlasts~48hours. Endometrialbloodflowreflectsproperlytheuterinereceptivitybecausetheendometriumisthesitewhereembryonicimplantationtakesplace. Therecentdiscoveryofmoleculescrucialforsuccessfulembryoimplantationhasofferedresearcherspreciousinsightintothisfield.Primaryadhesionmoleculesthatareimplicatedinimplantationincludeselectins,galectins,heparansulfateproteoglycans,MUC1,integrins,cadherins,etc. Integrinsareafamilyofcelladhesionmoleculesthathavenowbeenlargelyacceptedasmarkersofuterinereceptivity.Theirpatternofexpressionduringthemenstrualcyclesuggeststhatintegrinsmayalsoprovideameanstostudythefactorsthatregulatetheestablishmentofuterinereceptivityingeneral.Integrinsareafamilyoftransmembraneglycoproteins,formedbytheassociationoftwodifferent,non-covalentlylinked,αandβsubunits.Todate,18αandeightβchainshavebeenidentifiedinmammals.Whenpaired,theyform24distinctintegrinheterodimersthatdifferintheirfunction. Inthehumanendometrium,αvß3integrinplaysanimportantroleintheimplantationprocess&isawellcharacterizedbiomarkerofuterinereceptivity. Consideringtheliteratureonintegrinαvβ3expressionandregulation,thisproteinrepresentsapromisingclinicalandresearchmarkerofthehumanimplantationprocess. Theaimofthecurrentstudyistoassessendometrialthickness,subendometrialbloodflow,aswellasexpressionofalphavbeta3integrinintheendometrialglandsasmarkersofuterinereceptivityinwomenwithunexplainedinfertility. Thisstudyisacasecontrolstudy,conductedatAinShamsUniversityMaternityHospital.Itincludedtwogroupsofwomen:Theunexplainedinfertilitygroup,included35patientspresentedtotheinfertilityoutpatientclinicwithunexplainedprimaryinfertility;andTheFertilegroup,included35patientsvolunteerfertileparouswomenpresentedtothefamilyplanningclinicseekingcontraception.Onday7afterdetectionofurinaryLHsurge,transvaginalultrasoundscan(TVS)wasdoneformeasuringendometrialthickness,SubendometrialDopplervelocimetryindices.OnthesamedayofTVS,endometrialsamplesweretakenusingofficesuctionsamplerforimmunohistochemicaldetectionofthealphavbeta3integrinantibody.