溫醫(yī)大生殖醫(yī)學課件05受精卵和著床

FertilizedeggsandimplantationRen-shanGeTermGestationalAge(GA),ormenstrualage,isaclinicaltermusuallygiveninweeksanddaystodescribehumandevelopmenttimedfromthefirstdayofthelastmenstrualperiod(LMP).Forgestationalageinassistedreproductivetechnologypregnancy2weeksareaddedtothefertilisationdate.Thisclinicalagethereforediffersbyapproximatelytwoweeksfromtheresearchmaterialstimedfromfertilization(fertilizationageorconceptionalage).Fertilizationageorconceptionalage:weeksanddaystodescribehumandevelopmenttimedfromthefirstfertilization.ConceptusTheentireproductofconception,thatisallthestructuresderivedfromtheoriginalzygote.Thisincludesnotonlytheembryo,thenfetus,butalsotheplacentaandmembranecomponentsformedfromthisoriginalcell.Alltheconceptuscomponentsthereforealsosharethesamegeneticcontentformedbyfertilization.ZonapellucidaZonapellucida(eggcoat,oolemma,vitellinemembrane,Latin,zonapellucida=transparentzone)Aspecializedextracellularmatrixsurroundsthedevelopingoocyte(egg,ovum)withintheovaryandfollowingovulation.TheoocytesynthesizesandsecreteseachzonapellucidaglycoproteinZP1,ZP2andZP3whereitisassembledintotheinsolublezonapellucidamatrix.Theproteinshavedifferentrolesinfertilization.Followingfertilization,thezonapellucidaalsosurroundstheblastocystduringthefirstweekofdevelopment,fromwhichit"hatches".Thezonapellucidahasaroleinfertilization,spermbinding,preventingpolyspermy,blastocystdevelopmentandpreventingprematureimplantation(ectopicpregnancy).Blastocyst(Greek,blastos=sprout+cystos=cavity)Termusedtodescribethehollowcellularmassthatformsinearlydevelopment.Theblastocystconsistsofcellsforminganoutertrophoblastlayer,aninnercellmassandafluid-filledcavity.Theblastocystinnercellmassisthesourceoftrueembryonicstemcellscapableofformingallcelltypeswithintheembryo.Inhumans,thisstageoccursinthefirstandsecondweeksafterthezygoteformsasolidcellularmass(morulastage)andbeforeimplantation.Morula(Latin,morula=mulberry)Anearlystage(CarnegieStage2)inpost-fertilizationdevelopmentwhencellsdividerapidly(embryoniccellcycle)producingasolidmassofcells(12-15cells)witha"mulberry"appearance.Cellproliferationoccursstillenclosedwithinthezonepellucida.Thisstageisfollowedbyformationofacavityinthiscellularmass(blastocyststage).Inhumans,morulastageofdevelopmentoccursduringthefirstweekfollowingfertilization.blastomeres-thecellsresultingfromtheinitialroundsofmitoticdivisionofthezygote.Thesecellsbecomesmaller(incytoplasmicvolume)witheachdivision.coronaradiata-layeroffolliclecellsofcumulusoophorusremainingattachedtozonapellucidaofoocyteafterovulation.infundibulum-funnel-shapedinitialsegmentofuterinetube(oviductorFallopiantube)openingintoperitonealcavityandconnectedtotheampulla.Theperitonealopeningsittingovertheovary.innercellmass-theclumpofcellsfoundinsidetheblastocyst.Thesecellswillgointoformtheembryo,thesearethe"stemcells"(wehereaboutinthemedia)thataretotipotential,theycanformanytissueintheembryo.Matureoocyte-thefemalegermcellreleasedatovulationfromtheovary.ovulation-releaseoftheoocytefromthematurefollicle.parentalgenomes-themale(sperm)andfemale(oocyte)DNAwhichcontributestotheembryo'scells.polarbodies-3exclusionbodieswhichcontaintheDNAnotusedbytheembryo.Cnuclei-themale(sperm)andfemale(oocyte)nucleiwithinthefertilizedoocyte,priortotheircombinationtoformthenewembryo'snuclei.trophoblasts-(Gr.trophe=nutrition)outerlayerofcellsonblastocystthatwillgeneratetheembryonicpartoftheplacenta.uterinewall-thesiteofnormalblastocystimplantation.zygote-Thefirst(diploid)cellstagefollowingfertilizationofthe(haploid)oocytebythe(haploid)spermatozoa.Thisisthefirstcelloftheconceptuswhichwilldividemitoticallyinitiallyintotwoblastomeres. ReproductiveSystemTheterm“reproduction”usuallymeansformationofnewlivingentities,whichcloselyresembletotheparentspecies.Inhigheranimals,reproductionisaccomplishedbyactivitiesofbothsexualorgansofmaleandfemale.Theprocessesareverycomplexincludingproductionofspermsandova,sexualintercourse,fertilizationofovum,pregnancy,developmentoffetusandlactation.ReproductiveandHormonalFunctionsoftheMale Functionsoftestes:spermatogenesisinseminiferoustubulessecretehormones(testosteroneandinhibin).TwoCompartmentsintheTestisLeydigCellsintheInterstitiumSeminiferousTubuleDevelopmentofLeydigcell干TLC祖TLC幼TLC成年TLCCYP17A1CholesterolCholesterolCYP11A1TransportProgesterone(P4)Androstenedione(D4)HSD3BHSD17B3Pregnenolone(P5)Testosterone(T)LeydigcellSteroidogenesis

Dihydrotestosterone(DHT)SRD5A1AKR1C14EndocrineFunctionofTestesAndrogensTestessecreteseveralmalesexhormones,whicharecollectivelycalledandrogens,includingtestosterone,dihydrotesteroneandandrostenodione.Testosteroneissomuchmoreabundantthantheothersthatonecanconsideritthesignificanttesticularhormone.(1)Functionsoftestosterone1)Maintenanceofspermatogenesis2)Stimulationofdevelopmentofgenitalia.3)Developmentandmaintenanceofthemalesecondarysexualcharacteristics.4)Maintenanceoflibido.5)Effectonmetabolism.Testosteroneincreasesanabolismofprotein,especiallythatinmuscleandgenitalia,andcausesgrowthofthebonesinthethickness,depositionofcalciumsaltsaswellenhancementofproductionofredcells.2.InhibinInhibin,aglycoproteinwithamolecularweightof31,000-32,000,hasapotentinhibitoryeffectonFSHsecretionbypituitarygland.TheeffectofinhibinonhypothalamusisslightlyinhibitoryinGnRHsecretion.RegulationofTestisFunctionHypothalamic-Pituitary-TestisAxisGnRH(gonadotropin–releasinghormone)GnRHissecretedbyhypothalamusandtransportedtotheanteriorpituitaryglandinportalblood.ThefunctionofGnRHistostimulatethesynthesisandreleasethetwogonadotropins,LHandFSH.critinism,noGnRHsecretedduringthepuberty,nodevelopmentofthesexualorgans,noreproductiveability(2)LH(Luteinizinghormone)LHandFSHaresecretedbycellsintheanteriorpituitarygland.LHcausesinterstitialcellofLeydigtosynthesizetestosteronebyactivatingthecAMPsecondmessagesystemandtoreleasetestosterone.(3)FSH(folliclestimulatinghormone)FSHstimulatesSertoilcellstoproduceABP(androgenbindingprotein).ABPbindswithtestosteroneandenterstheseminiferoustubule,increasingtheandrogenconcentrationintubuleandpromotingspermatogenesis.FSHstimulatesSertoilcelltoproduceandsecreteinhibin,whichplaysanegativefeedbackmechanismforcontroloftestisfunction.2InhibinInhibinhasastrongdirecteffectontheanteriorpituitaryglandininhibitingFSHsecretionandalighteffectonthehypothalamusininhibitingGnRHsecretion.Theseautomaticfeedbackmechanismscanmaintainanormalspeedofspermatiogenesis,whichisrequiredformalereproductionfunction.ReproductiveandHormonalFunctionsoftheFemaleDayMenstrualcycleEvent

1MenstrualPhaseMenstrualCyclechanges:Uterineendometrium(loss),Ovary(FollicleDevelopment)2

3

4

5ProliferativePhaseMenstrualCyclechanges:Uterineendometrium(proliferation),Ovary(FollicleDevelopment)67

Week-2:GA,ClinicalWeek1Ovaries–2femalesexglandsProduceeggcellsProducesthehormone,estrogenUterusorWombMuscularpear-shapedorganWherebabydevelopsFallopianTubes

Eggtravelsthroughthese2tubestotheuterusCervix

Openingbetweentheuterus&vaginaVagina

MusculartunnelfromcervixtooutsideMenstruation,OvulationandHormonalRegulationThenormalreproductiveyearsofthefemalearecharacterizedbymonthlyrhythmicalchangesofsecretionofthefemalehormonesandcorrespondingchangesintheovariesandsexualorgans.Thisrhythmicalpatterniscalledthefemalesexualcycleofmenstrualcycle,whichmayberegardedasperiodicpreparationforfertilizationandpregnancy.Itsmostconspicuousfeatureistheperiodicvaginalbleedingthatoccurswiththesheddingoftheuterinemucosa,whichisknownasmenstruation.Thelengthofamenstrualcycleisabout28days.DiagrammaticsectionoftheovaryshowingvariousstagesinthelifeofaGraafianfollicle:aprimaryoocytedevelopingintoafullymaturefollicleabouttoovvlate,thenturningintoacorpusluteumandfinallyendingupasacorpusalbicans.OvarianCycle(1)Follicularphase;(2)Ovulation;(3)LutealphasePhasesofendometrialgrowthandmenstruationduringeachmonthlyfemalesexualcycle.2.UterinecycleandmenstruationProliferativephase(estrogenphase)Secretoryphase(progesteronephase)MenstruationII.EndocrineFunctionsofOvariesFunctionsofEstrogenOnsexualorgans.Theprinciplefunctionofestrogenistocausecellularproliferationandgrowthofthetissuesofthesexorgansandothertissuesrelatedtoproduction.Estrogenstimulatesthedevelopmentofsexualorgansincludingovaries,fallopiantubes,uterus,vaginaandtheexternalgenitalia.(2)Onsecondaryfemalesexualcharacteristics.Estrogenstimulatesdevelopmentofthesecondarysexcharacteristicsoffemalesuchasfemininefigure,softandsmoothskin.Itcausethebreasttogrowandtoshowmatureappearance.(3)Onmetabolism.Estrogencausesaslightincreaseintotalbodyprotein,whichresultingrowth-promotingeffectonthesexualorgans,thebones,thebreastsandafewothertissues.Estrogenhasaslighteffectonretentionofwaterandsodiumbythekidneytubules.2.ProgesteroneFunctionsofprogesteroneEffectonuterus.Byfarthemostimportantfunctionofprogesteroneistopromotesecretarychangesintheuterineendometrium,thuspreparingtheuterusforimplantationofthefertilizedovumandprovidingnutritionfortheearlydividingovum.Progesteronedecreasesexcitabilityandsensitivitytooxytocinofmyometrium.Itdecreasesthefrequencyandintensityofuterinecontractions,therebyhelpingtopreventexpulsionoftheimplantedovum.(2)Effectonbreasts.Progesteronepromotesdevelopmentofthetubulesandalveoliofthebreasts,causingthealveolarcellstoproliferate,enlarge,andbecomesecretarynaturebutnottosecretemilk.(3)Thermogeniceffect.Progesteronecausesthermogeniceffectandisresponsiblefortheriseinbasalbodytemperatureatthetimeofovulation.(4)Progesteronerelaxesthesmoothmuscleofthebloodvesselsanddigestivetracts.III.HormonalcontrolofthemenstrualcycleMenstrualCycleAwomanisbornwithallthefolliclesshewillhave(~400,000).Mostwillnotmature,~400willLHandFSHinfluencedevelopingfollicle,whichproducesestrogen(inparticular,estradiol).AnincreaseinestrogenresultsinpeaklevelsofFSHandLHwhichtriggerovulation(positivefeedbackloop).Ovulationoccurs–ovumrupturesfromdominantfollicle.HighLHlevels12-36hrsbeforeovulationmarkdivisionoffollicularandlutealphases.MenstrualCycleLutealphase:folliclechangesintoatemporaryendocrineorganknownascorpusluteumSecretesseveralhormones,includingprogesterone,whichhelpspreparetheliningoftheuterusforimplantationshouldtheeggbefertilizedInabsenceoffertilization,theendometrialliningshedsduringmenstruation.MenstrualCycleIffertilizationoccurs,thecorpusluteumcontinuestosynthesizeandsecretesteroidhormonesthatmaintainpregnancyforthefirst4-6weeks.Aidedbyanotherhormone,humanchorionicgonadotropin(hCG),thatisbiologicallysimilartoLH.hCGissecretedbycellsintheconceptusdestinedtobecometheplacentamenstrualcycleFSHLHestrogenprogesteroneendometriumproliferativeuterussecretoryuterus

proliferativephase1.stimulatedbyestrogen2.rebuildsendometrium

secretoryphase1.stimulatedbyestrogenandprogesterone2.endometriumpreparesforimplantation

menstrualphase1.lackofestrogen/progesterone2.removesendometriumFig.34-1:EventsoftheMenstrualCycle

GraafianfolliclestimulatedHypothalamussecretesGnRHHighestrogenlevelsinhibitFSHsecretion,stimulateLHproductionAnteriorpituitarysecretesLHandFSHLHmakescorpusluteumsecreteprogesteroneOvariesreleaseestrogenDecreasedLHandFSHlevelsProgesteroneinhibitsLHsecretionDecreasedestrogenandprogesteronelevelsstimulateGnRHsecretionLHmakesmaturefollicleburst:ovulationCorpusluteumatrophies,stopsmakingprogesteroneFollicular

stageLutealstageProliferativephaseSecretoryphaseMenstrualphaseCyclicchangesinovarianhormonessecretionalsocausecyclicchangesinbasaltemperature.OntheayoftheLHpeak,whenestrogensecretionbeginstodecline,thereisaslightdropinbasalbodytemperature.StartingaboutonedayaftertheLHpeak,thebasalbodytemperaturesharplyrisesasaresultofprogesteronesecretionandremainselevatedthroughoutthelutealphaseofthecycle.Thedayofovulationcanbeaccuratelydeterminedbythismethod,makingthemethodusefulinincreasingfertilityifconceptionisdesired.Sincethedayofthecycleinwhichovulationoccursisquitevariableinmanywomen,however,therhythmmethodisnotreliableforcontraceptionbypredictingwhenthenextovulationoccur.FertilizationandImplantationFertilizationandImplantation(Movie)Summaryofearlydevelopmentinthefirstweekfollowingfertilization

Theconceptusproceedsthroughembryoniccellcycleroundsofmitosisstillenclosedwithinthezonapellucida.Progressingfromazygote,toblastomeres,thentoamorulaandfinallytoablastocyst.Theuterinetubeepitheliumconsistsofciliatedcellsthataremovingthesecretedfluidtowardstheuterinebody.Theconceptusisfloating"boat-like"withinthisfluidandmovedinthesamedirection.Towardstheendofthefirstweektheblastocysthasreachedtheuterinebodyandfromaboutday5onwards,theblastocyst"hatches"fromthesurroundingzonapellucida.Theconceptuscannowreceivenutritiondirectlyandcancommencetheprocessofimplantationinweek2.StagesofhumandevelopmentFollicleSpermFertilizationSpermatozoapenetratesthezonepellucida(ZP).Spermatozoaswimsaroundtheperivitellinespace(PVS).Spermatozoaswimsaroundtheperivitellinespace(PVS).Spermatozoahitsthefirstpolarbody(1pb).Spermatozoabindstheoocytemembrane.Secondpolarbody(2pb)extrudesandthefertilizationconeforms.1.Thefirstdiploidcellthatformsfollowingfertilizationbyfusionofthehaploidoocyte(egg)andspermatozoa(sperm)resultinginthecombinationoftheirseparategenomes.FusionTheimageshowsthecellwiththe2pronucleistillpresentbeforefusionenclosedwithinthezonapellucida.Inhumans,thiscellthenundergoesaseriesofmitoticcelldivisions,stillenclosedwithinthezonapellucida,duringthefirstfewdaysofdevelopmenttoform2blastomeresthenasolidcellmasscalledthemorula.Thesepronucleiarethenucleifromthespermatozoa(sperm)andoocyte(egg)andcontainallthenucleargeneticmaterial(chromosomes,DNA,genes).Twooftheegg'spolarbodies(right,3o'clockpositionofimage)areshownattheedgeoftheeggcytoplasm.ThesepolarbodiescontaintheexcessDNAfromthemeioticdivisionsoftheegg.Thezonapellucida(edgeofimage)formsaspecializedthickextracellularmatrixlayeraroundboththeeggandthedevelopingconceptusforthefirstweek.Mitochondriainthecytoplasmcontainadditionalgenesandinhumansthesemitochondrialgenesareentirelyderivedfromtheoocyte.Distributionofthepericentromeres,centromeres,andrDNAFISHsignalsinlate1-cellstageembryos(fluorescentand3Dreconstruction).TranscriptionofribosomalDNA(rDNA)isswitchedoffinearlymouseembryosandnucleoliarenotpresent.MostrDNAsignalsarearoundtheNucleolar-PrecursorBodies(NPBs),thoughsomesignalsassociatedwithpericentromericfilaments(extendingfromtheNPBstowardsthenuclearperiphery)aswellasrDNAsignalsjoiningtwoNPBs.1-cellembryosatthePN4stage(fertilizationoccurredatabout12afterhCGinjection(hphCG);zygotecollectedat27hours)red-pericentromericprobesgreen-ribosomalDNAprobesgrey-DNAcounterstainedwithYopro-1Mousezygotesmalepronucleuscontains5-hydroxymethylcytosine(5hmC)formedbyenzymaticoxidationof5-methylcytosine(5mC).A-Amousezygotewasdouble-stainedwithanti-5hmCantibody(green)andanti-5mCantibody(red).Thesmallermaternalpronucleusisclosertothepolarbody(pb).Abright-fieldimageisshownonthefarleft.MouseZygotePaternalGenomeReprogrammingB-Additionalzygotesweredouble-stainedwithanti-5hmCantibody(green)andanti-5mCantibody(red).Mergedimagesareshown.C-Zygotesobtainedbyinvitrofertilizationweredouble-stainedsimilarly.Twopolyspermiczygotes(totheright)exhibit5hmCstainingintwopaternalpronuclei.D-5mCand5hmCstainingrevealtwoseparatechromosomesetsatmetaphaseofzygotedivision.Aconfocalimageisshown.E-Individualchromosomesarelargelystainedforeither5mC(likelyoriginatedfromthematernalpronucleus)or5hmC(likelyfromthepaternalpronucleus)atanaphaseofzygotedivision.TwoZsectionsofthesamezygoteareshownDay1-zygote,thefirstdiploidcell.Day2-2then4blasomeres,thefirstcellsformedbymitoticcelldivision.Day3-morula.Day4-compactingmorula.Day5-blastocyst.Day6-hatchingblastocystfromzonapellucidashell,afterthiseventtheblastocystcannowattachandimplantintotheuterinewall.CelldivisionII.HormonesofPlacentaTheplacentaformslargequantitiesofhumanchorionicgonadotropin,estrogen,progesteroneandhumanchorionicsomatomammotropin,whichareallessentialtoanormalpregnancyHumanChorionicGonadotropin(HCG)HCGisaglycoproteinwithamolecularweightof39,000.Itissecretedbythesyncytialtrophoblastcellsandcanbemeasuredintheblood8to9daysafterovulation.Therateofsecretionrisesrapidlytoreachmaximumbout10to12weeksafterovulationanddecreasestomuchlowervalueby16to20weeksafterovulation.Itcontinuesatthislevelfortheremainderofpregnancy.ThishormoneisidenticaltoLHinitseffectandthereforeisabletomaintainthecorpusletumpastthetimewhenitwouldotherwiseregress.Thesecretionofestradiolandprogesteroneisthusmaintainedandmenstruationisnormallyprevented.Diagnosisoftheearlypregnancy2.ProgesteroneandEstrogenAtthefifthtosixthweekthemother’scorpusluteumbeginstoregress(eveninthepresenceofhCG),butbythistimetheplacentaissecretingmorethansufficientamountsofsteroids(estrogenandprogesterone)tomaintaintheendometriumandpreventmenstruation.Duringpregnancy,theextremequantitiesofestrogencauseenlargementofuterus,breastsandmother’sfemaleexternalgenitalia,whichareconvenienttdevelopingoffetus.Progesteronehasaspecificeffectodecreasingthecontractilityofpregnantuterus,thuspreventinguterinecontractionsfromcausingabortion.3.HumanChorionicSomatomammotropin(HCS)HCSisaproteinwithmolecularweightof38,000.Itbeginstobesecretedbytheplacentaatthe5thweekofpregnancy.SecretionofHCSincreasesprogressivelythroughouttheremainderofpregnancyindirectproportionttheweightofplacenta.HCSmainlystimulatesgrowthoffetusandregulatesmetabolismofcarbohydrate,fatandproteininboththefetusandthemotherImplantationTheterm"implantation"isusedtodescribeprocessofattachmentandinvasionoftheuterusendometriumbytheblastocyst(conceptus)inplacentalanimals.Inhumans,thisprocessbeginsattheendofweek1,withmostsuccessfulhumanpregnanciestheconceptusimplants8to10daysafterovulation,andearlypregnancylossincreaseswithlaterimplantation.Theimplantationprocesscontinuesthroughthesecondweekofdevelopment.AdplantationTheinitialphaseoftheimplantationprocessis"adplantation".Thisfirstphaserequiresthenewlyhatchedblastocysttolooselyadheretotheendometrialepithelium,often"rolling"totheeventualsiteofimplantationwhereitisfirmlyadhered.Thisprocessrequiresboththeblastocystadhesioninteractionwiththeendometriumduringthe"receptivewindow".Subsequentdevelopmentoftheplacentaallowsmaternalsupportofembryonicandfetaldevelopment.Ifimplantationhasnotproceededsufficientlyduringthemenstrualcycletoallowhormonalfeedbacktotheovary,thenthenextcyclemaycommenceleadingtoconceptusloss.Thereisalsoevidence,fromanimalmodels,thataconceptuswithmajorgeneticdoesnotdeveloporimplantcorrectlyleadingtotheirlossduringthefirstandsecondweeksofdevelopment.EndometrialReceptivityInhumans,receptivityoccurs6daysafterthepost-ovulatoryprogesteronesurgeandlastsabout2to4days(aboutdays20to24ofthemenstrualcycle).Asimilar"receptivitywindow"occursfollowingfertilizationinotherspecies:ratday5andmouseday4.5.ManystudieshavelookedintoidentifyingmarkersforthisreceptivityperiodbothtooptimizeandtoblockthisprocessImplantationTheuteruslining(endometriumepithelium),thehatchedblastocystwithaflatouterlayeroftrophoblastcells(green),theinnercellmasswhichhasformedintothebilaminarembryo(epiblastandhypoblast)andthelargefluid-filledspace(blastocoel).greencells-trophoblastlayeroftheconceptus.blue

cells-epiblastlayerofthebilaminarembryo.yellowcells-hypoblastlayerofthebilaminarembryo.whitecells-uterineendometriumepithelium.red-maternalbloodvesselThesecondweekofhumandevelopmentisconcernedwiththeprocessofimplantationandthedifferentiationoftheblastocystintoearlyembryonicandplacentalformingstructures.Implantationcommencesaboutday6to7Adplantation-beginswithinitialadhesiontotheuterineepitheliumblastocystthenslowsinmotility,"rolls"onsurface,alignswiththeinnercellmassclosesttotheepitheliumandstopsImplantation-migrationoftheblastocystintotheuterineepithelium,processcompletebyaboutday9coagulationplug-leftwheretheblastocysthasenteredtheuterinewallday12NormalImplantationSites-inuterinewallsuperior,posterior,lateralUterineepithelialciliaareresponsiblefortheinitialmovementoftheooycteandconceptus(zygote,morula,blastocyst).Inhumans,thisisduringthefirstweekofdevelopment.Uterineepithelialmicrovilliareinvolvedwiththeimplantationprocess.Hormones(estrogenandprogesterone)regulatebothciliaandmicrovilli.Thedifferencesinsizeandshapeofciliaandmicrovilliarewellillustratedbyscanningmicrographsofthelumenalsurfaceoftheepitheliumliningthemammalianoviduct.Thetuftsofciliaassociatedwithindividualciliatedcellsprojectseveralmicronsabovetheconvexapicesofnonciliatedcellscoveredwithshortmicrovilli.Thenumberofciliatedcellsinthisepitheliumisunderhormonalcontrolbyestrogens.CiliaMicrovillilongprocessesepithelialcellapicalmembranespecializationsmicrotubulefilledmotilestructureshortprocessesepithelialcellapicalmembranespecializationsmicrofilamentfillednon-motilestructureUterodomesorPinopodsCellularfeatureseenontheapicaluterineepitheliumsurface.Thepresenceofthesestructuresisthoughtinmanyspeciestobeamarkerforendometrialreceptivity.Inhumansthough,recentstudieshaveshownpinopodesarealsopresentthroughoutthelutealphaseofthemenstrualcycle.Ithasalsobeensuggestedthattheirroleisnotprimarilypinocytotic,hencethealternatesuggestedname"uterodomes"basedupontheirappearancewhenimagedbyelectronmicroscopyThesetransientmicroprotrusionsinter-digitatewithmicrovilliontheapicalsyncytiotrophoblastsurfaceoftheblastocystduringinitialadplantationandimplantationprocess.ScanningelectronmicroscopeimagesoftheendometrialsurfaceofaDay13pregnantsow.(A)and(B)Tissuefrombetweenattachmentsites.(C)and(D)Tissueatattachmentsites.uterodomes(pinopods)Cellularfeaturesseenontheapicaluterineepitheliumsurface,thesemicro-protrusionsinter-digitatewithmicrovilliontheapicalsyncytiotrophoblastsurfaceoftheblastocystduringadplantationandimplantationprocess.InhibitoryInteractionsTheepithelialsurfacehasanassociatedglycocalyx,thecellsurfaceformedbytransmembraneandsecretedglycoproteins.Mucinsareamajorcomponentsandmucin1(MUC1),atransmembraneproteinappearstohavedualroles.Firstly,actingasabarriertobothmicrobialinfectionandenzymaticattack.Secondly,itsexpressionisalteredbyhormonesanddecreasedMUC1expressionassociatedwithreceptivity.Thissuggeststhathighlevelsofmucinareinhibitorytoimplantation.Interestinglythesameproteinishighlyexpressedlaterintheplacentalamnion,whereitsanti-bacterialandanti-adhesiverolesareagainrequired.LegendAA-arachidonicacidBMP2-bonemorphogeneticprotein2cPLA2α-cytosolicphospholipaseA2αCOUP-TFII-chickenovalbuminupstreampromotertranscriptionfactor-2Cox2-cyclooxygenase-2E-estrogensEC-epithelialcell(luminalandglandularepithelia)ENaC-epitheliumsodiumchannelER-estrogenreceptorErbB1/4-epidermalgrowthfactorreceptor1/4ERK-extracellularsignal–regulatedkinaseFGF-fibroblastgrowthfactorGE-glandularepitheliumgp130-glycoprotein130Hand2-heart-andneuralcrestderivatives-expressedprotein2HB-EGF-heparin-bindingepidermalgrowthfactor-likegrowthfactorHoxa10/11-homeoboxA10/11ICM-innercellmassIHH-IndianhedgehogKLF5-Kruppel-likefactor5LIF-leukemiainhibitoryfactorLIFR