医学遗传与胚胎发育:7.1Human Embryology-1

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1、WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?FromFatherFromMotherWheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?WheredidIcomefrom ?Wherearewefrom?WheredidIcomefrom

2、?WheredidIcomefrom ?Humanembryologyissciencefocusedontheresearchesofontogenesis,developmentanditsvariationforhumanbody.ConceptInclusionsHumanEmbryologyPeriodoffertilizedovumorzygotetoblastocystFertilizationbeginningtothesecondweekend:includingfertilization,cleavage,blastocystformationandbeginningofi

3、mplantationPeriodofembryogenesisThethirdweektoeighthweekends:embryonicdiscformation,andprimordiaofprincipalorgansestablishmentandprimitivehumanbodysettingFetalperiodTheninthweektoparturitionPerinatalperiod:the28thweekto1stweekafterbirth.TimeofBirth266daysEarlyStagesofDevelopmentinHumanEmbryoItindica

4、testhetimebetweenbeginningoffertilizationto8thweekendforprimitivehumanbodysetting,includinggameteandfertilization,cleavageandformationofblastocyst,implantation,embryonicdiscformationanddifferentiation,fetalmembraneandplacenta,including:Pre-embryoperiodandperiodofembryogenesis.1.Thepreparationofferti

5、lizationGermcellsdevelopmentandmaturationFertilizationCompositionReproductiveglandtestisGenitalductsepididymis,vasdeferens,ejaculatoryduct&urethraAccessorysexglandsprostategland,seminalvesicle&bulbourethralglandExternalgenitalorganspenis&scrotumMaleReproductiveSystemFunctionTestisproducespermatozoa&

6、secreteandrogenReproductivetractspermmaturation,nutrition,storage&transportationAccessoryglandsThesecretionstoformseminalplasmaSeminiferousTubulesSeminiferousepitheliumSpermatogeniccells(5-8layers)Sertolicells(only1layer)BasementmembraneTheoutsideofbasementmembranemyoidcell,collagenousfibertoformlim

7、itingmembraneTestisspermatogoniaprimaryspermatocytessecondaryspermatocytesspermatidsspermatozoaSpermatogenicCells1.SpermatogoniumCellisrelativesmallinsize,situatednexttothebasallamina.46xy,2nDNA,mitosisAType(AdAp)BTypeAdType:nucleusshowsovalshapeanddarkstaining,belongtostemcellApType:nucleusshowsova

8、lshapeandlightstainingBType:roundnucleusandroughchromatinprimaryspermatocyte2.PrimarySpermatocyteThelargestcells,severallayersLargeandroundnucleus,darkstaining,roughorgranularchromatin46xy,4nDNAFirstmeioticdivisionsecondaryspermatocyte3.SecondarySpermatocyteAdjacentlylocalizedinthelumenofseminiferou

9、stubules,smallinsize,short-livedcellsRoundnucleus,darkstaining23xor23y,2nDNASecondarymeioticdivisionspermatid4.SpermatidJuxtaluminallocationwithintheseminiferoustubules,distinguishedbytheirsmallinsize,nucleiwithareasofcondensedchromatin(roundnucleitoflatnuclei)Cellsinroundshape inelongatedshape23xor

10、23y,1nDNATransformingtospermatozoa4.SpermatidSpermiogenesisanditsprocedureNucleusflatshapeandcondensed,GolgiapparatusacrosomalvesicleacrosomeCentrioleflagellumMitochondriagraduallymovetowardtheflagellumandarrangethemselvesasaspiralaroundthemiddlepiecesheathofmitochondriaCytoplasmresidualbodiessheddi

11、ngSpermiogenesis 贺忆培,季颖婕,黄敏,丁之德。贺忆培,季颖婕,黄敏,丁之德。精子变形中相关蛋白的精子变形中相关蛋白的研究进展研究进展。国际生殖健康国际生殖健康/ /计划生育杂志计划生育杂志 2014;2014; 33(6):432-43633(6):432-436 基金资助基金资助 上海交通大学医学院第七期大学生科学创新项目上海交通大学医学院第七期大学生科学创新项目 (20120092012009););第七期国家大学生科学创第七期国家大学生科学创新项目。新项目。 作者单位作者单位 上海交通大学医学院上海交通大学医学院 20112011级临床医学八年制级临床医学八年制Sper

12、matogenesis&structureofhumanspermatozoon5.SpermatozoonTadpole-shaped,length60m,head(5m)andtail5.SpermatozoonHeadNucleus(DNA);Acrosome:covered2/3nucleus,containingacrosinandseveralotherproteolyticenzymesFertilization5.SpermatozoonTailAxoneme(9+2microtubules)motilityFourpiecesNeck,middlepiece,principa

13、lpieceandendpieceNeck:short,ContainingcentrioleMiddlepiece:spermaxoneme,outercondensedfibersheath,mitochondrialsheathprovidingenergy5.SpermatozoonTail5.SpermatozoonTailPrincipalpiece:length45m,spermaxoneme,outercondensedfibersheathEndpiece:spermaxonemeSpermatogenesisDefinitionSpermatogoniaspermatozo

14、a(64days)Synchronousdevelopment 1.SpermatogoniaproliferationMitosisAdApBprimaryspermatocyte(46XY,4nDNA)2.Spermatocytemeiosis23X/23Y,2nDNA23X/23Y,1nDNA3.Spermatidtransformation(spermiogenesis)NochangingbothinDNAandchromosomespermatozoa(23X/23Y,1nDNA)SpermatogenesisinthreeperiodsSpermatogenesisSpermat

15、ogenicCellsSpermatogonia:ATypeBTypeATypedifferentiationMitosisPrimarySpermatocytes:46XYSecondarySpermatocytes:23X/23YSpermatid:23X/23YSpermatozoa:23X/23YSpermiogenesisSpermatogenesisSertoliCellsMorphologicalStructureLMElongatedpyramidalcells,partiallyenvelopspermatogeniccells.Cellsadheretothebasalla

16、mina,whiletheirapicalendsfrequentlyextendintothelumenoftheseminiferoustubule.Cytoplasmappearspoorlydefined.Nucleusistriangleorirregular,andpalestainingandnucleolusisobvious.EMOrganellesarewelldevelopedincludingRER,SER,Mitochondria,Golgiapparatus,lysosome,microtubuleµfilament.Tightjunctionsextra

17、tubularcompartmentandintratubular(adluminal)compartment.FunctionSupport,protection,andnutritionalregulationofdevelopingspermatozoa,Phagocytosis:residualbodies,SynthesizeandsecreteInhibitin,Secretetesticularfluidtotransportspermatozoa,Secreteandrogen-bindingprotein(ABP)highconcentrationofandrogenwith

18、inseminiferoustubulesfacilitatethespermatogenesisBuilduptheblood-testisbarriertoprotectthedevelopingspermcellsfromimmunologicattackLeydig(Interstitial)CellsLocalization Agroupofthecellshavecharacteristicsofsteroidsecretorycell,adjacenttothebloodandlymphaticvessels.StructuresLMRoundedorpolygonalinsha

19、pe,acentralnucleusandaeosinophiliccytoplasmrichinsmalllipiddroplets seminiferousepitheliumspermatogenesisT bloodsecondarysexualcharacteristicslibido(sexualfunction)developmentofgenitalorgansFunctionsynthesizeandsecreteandrogenEMRichinSER,Thecristaeofmitochondriashowtubularinshape,Containinglipiddrop

20、letsMr.ArnoldSchwarzeneggerSeminiferousEpithelium&TesticularInterstitiaReteTestis,DuctuliEfferentes(EfferentDuctules)andDuctusEpididymisCaput efferentductpseudostratifiedcolumnarepitheliumLumenisirregularinshape,containingtallcolumnarciliatedcellsandshortcolumnarnon-ciliatedcells.Corpus&Caudaepididy

21、malductpseudostratifiedcolumnarepitheliumLumenisregularinshape,containingtallcolumnarciliatedcells( (stereocilium)andbasalcells.Functionspermatozoastorageandmaturation,synthesizeandsecretebioactivemolecules,e.g.carnitine,glycerophosphorylcholine,sialicacidandtestosterone.Epididymis Caput,CorpusandCa

22、udafromEpididymisDuctuliEfferetes(EfferentDuctules)fromEpididymisMucosapseudostratifiedciliatedcolumnarepitheliumlaminapropria:richinelasticfibersplica:longitudinalfoldsMuscularissmoothmuscle,thick,innerlongitudinal,middlecircular,outerlongitudinalAdventitiaC.T. DeferentDuctAccessorySexGlandsprostat

23、eglandseminalvesiclebulbourethralglandSecretionstoformseminalplasmaComposedbyspermatozoaandseminalplasma,milkycolor,pH7.2Normalvolume:1.41.7mL/perejaculation,15M/mL,alivesperm58%,spermmotility40%,forwardmotility32%,normalmorphologicalsperm4%(WHO5th)Ifthespermamountandmotilitydecline,andabnormalmorph

24、ologicalspermincreaseorelementsinseminalplasmachangesleadingtomaleinfertilitySemenPollutionandMaleInfertilityMeekerJD,et al.Reprod Toxicol 2010LiDK,et al.Fertil Steril 2010BisphenolAPollutionandMaleInfertilityMendiolaJ,et al.J Androl2011 di(2-ethylhexyl)phthalate(DEPH)DEPHandBPA周婉格,王统菲,周周婉格,王统菲,周 任任

25、 综述;丁之德综述;丁之德 审校。审校。 DEHPDEHP对哺乳对哺乳动物生殖系统影响的研究进展;动物生殖系统影响的研究进展;国际生殖健康国际生殖健康/ /计划生育杂计划生育杂志志2013; 32(1):50-542013; 32(1):50-54李李 倩倩, , 应应 倩倩 综述;丁之德综述;丁之德 审校。审校。双酚双酚A A对哺乳动物生殖对哺乳动物生殖系统影响的研究进展;系统影响的研究进展;国际生殖健康国际生殖健康/ /计划生育杂志计划生育杂志2012; 31(6):46-50 2012; 31(6):46-50 作者单位作者单位: : 上海交大医学院上海交大医学院0909级临床医学八年制

26、级临床医学八年制 基金资助:基金资助:上海交通大学医学院第五期大学生创新项目上海交通大学医学院第五期大学生创新项目 (20110252011025););第五期上海市大学生创新第五期上海市大学生创新训练项目。训练项目。MaleObesityandInfertilityYueLiu,YiGuoZhideDing*.Proteomicpatternchangesassociatedwithobesity-inducedathenozoospermia.Andrology2015;3(2):247-59*CorrespondingauthorYueLiu,WenzhenZhao,ZhideDing*

27、.Palmitoyl-ProteinThioesterase1(PPT1):AnObesity-InducedRatTesticularMarkerofReducedFertility.Mol Reprod Dev 2014;81:55-65*CorrespondingauthorObesityandMaleInfertilityObesityandMaleInfertilityFanY,DingZ*.Diet-inducedobesityinmaleC57BL/6micedecreasesfertilityasaconsequenceofdisruptedblood-testisbarrie

28、r.PLoS One 2015; 10(4):e0120775. *CorrespondingauthorMaleFertilityTheyoungestfatherTheoldestfatherMaleContraceptivePills(2012)CompositionandFunctionOvaryproduceoocyte,synthesizeandsecretefemalesexualhormonesOviducttransportoocyte,thesiteforfertilization UterusfetusgrowthVaginaandVulvaMammaryglandsba

29、byfeedingFemaleReproductiveSystemGeneralStructureSurfaceasinglelayerofsquamousorcuboidalcellsTunicaalbugineaathinlayerofdenseconnectivetissueCortexouterpart,thick,CT,oocytesindifferentstages,reticularfibersandstromacellsMedullacentralpart,CT,richinbloodvesselsandelasticfibersaswellasnervesHilusvesse

30、lsandnervereachandleave,CT,hiluscells,androgensecreting,smoothmusclesOvaryAmodelforovarystructureFollicleoocyte+follicularcells1.PrimordialFolliclesuperficiallayerofcortex,alargeamountofcells,ball-shapePrimaryoocyte resultsofmitosisofoogoniumandenteringintothephaseoffirstmeiosis,andstopinthestageofp

31、rophase,30mindiameter,cellsinroundshape,lightstaining,prominentnucleolus,eosinophiliccytoplasmcontainingcorticaloocytegranulesFollicularcells asinglelayerofsquamouscells,smoothsurface,celljunctionsbetweentheprimaryoocyteandfollicularcells,athinlayerofbasalmembraneoutside FollicleDevelopment&Maturati

32、on2.GrowingFollicle(1)PrimaryFollicleprimaryoocyteincreaseinsize,50-80mfollicularcellsasinglelayerofsquamouscellscuboidalcellsorseverallayerszonapellucida:betweentheprimaryoocyteandfollicularcellssperm-oocyterecognitionthecafolliculithecainternaandthecaexternaZonaPellucida(ZP)betweentheprimaryoocyte

33、andfollicularcells,ahomogeneouseosinophilicmembraneofglycoproteinPrimaryoocyteFSHstimulating,increaseinsize,125-150m,ZP5mFollicularcells antrumfolliclecontainingfollicularfluid, composedofsecretoryfluidfromfollicularcellsandpenetratedfluidfrombloodvesselsofthecafolliculi,cumulusoophorus, ,coronaradi

34、ata,granulosacellstoformzonagranulosa. (2)SecondaryFollicle granularcells primaryoocyteSecondaryFollicle(TEM)3.MatureFollicle(TertiaryFollicleorGraafianFollicle) Theterminalstageoffolliculardevelopment,thefullsizeof25mm,abulgeonthesurfaceoftheovary(stigma),accumulationoftheliquorfolliculi,enlargedan

35、trum,zonagranulosabecomingprogressivelythinner3.MatureFollicle Beforethe36-48hrsofovulation,primaryoocytecanfinishthefirstmeiosis,formingsecondaryoocyteandthefirstpolarbody,localizedinperivitellinespace(betweenthesecondaryoocyteandZP).Thechromosomeisdividedintohalfforeach(23,X).Then,secondaryoocytei

36、mmediatelyenterthesecondarymeiosisandstopinthemetaphase.ERp57andOocyteMaturationYueLiu,YeminZhu,XiaohuiWu,ZhideDing*.IncreasedExpressionofERp57inRatOocytesDuringMeioticMaturationIsAssociatedWithSperm-EggFusion.Mol Reprod Dev2014;81:315-325*CorrespondingAuthorEpigeneticsinGameteandFetusDevelopments李美

37、姿、姜梦迪、黄楷李美姿、姜梦迪、黄楷 综述;丁之德综述;丁之德 审校。审校。表观遗传学与哺乳动物配子表观遗传学与哺乳动物配子和胚胎发生发育的研究进展;和胚胎发生发育的研究进展;中国男科学杂志中国男科学杂志2015; 29(1): 63-66 2015; 29(1): 63-66 作者单位作者单位: : 上海交大医学院上海交大医学院20122012级临床医学专业级临床医学专业基金资助:基金资助:上海交通大学医学院第八期大学生创新项目(上海交通大学医学院第八期大学生创新项目(20140112014011) Primaryoocyte(46,XX2nDNA) firstmeiosisFirstpol

38、arbody+Secondaryoocyte(23,X2nDNA)metaphaseinsecondarymeiosisfertilizedunfertilizedsecondarymeiosisfinishSecondarypolarbody+matureoocyteDegeneration(23,X1nDNA)4.TheSynthesisofEstrogenDuringtheoocytedevelopment,estrogencanbesynthesizedandsecretedbycellsfromboththecagranulosaandthecainterna.Thecellsoft

39、hecainterna(LHR)takecholesterol(blood),synthesizeAndrogen(aromatase)granulosacells(FSHR&LHR)Estrogenantrumfolliculiandbloodcirculationtargetcellsandtissues Fourteendaysbeforetheexpectedonsetofthenextmenstruation,theserumlevelofluteinizinghormone(LH)reachapeak.Enzymesofthefollicularfluidleadtoaruptur

40、eofthethinfollicularwall,andthesecondaryoocyte,withitscoronaradiataandtheliquorfolliculiandZP,arereleasedintothepelviccavityandsweptintotheoviductbyitsfimbriatedfunnel. OvulationAmodelforovulationofmaturefollicleOvaryOocyte OvulationCorpusLuteumFormation&DegenerationAfterovulation,therupturedfollicl

41、ecollapses,anditsholeisfilledbyahemorrhage.Followingseveraldays,itbecomesacellmasswithyellowcolorunderfreshconditionandsecretsthesteroidhormones.Granulosaluteincells derivedfromgranulosacells,polygonalshape,increaseinsize,lightstaining,localizedincentralpartofcorpusluteum,secretingprogesteroneandrel

42、axinThecaluteincells derivedfromthecellsofthecainterna,smallinsize,darkstaining,localizedinperipheralpartofcorpusluteum,secretingestrogen(togetherwithgranulosaluteincells)CorpusLuteumL.M.(thecaluteincellsgranulosaluteincells)TheChangesinCorpusLuteumIfoocyteisnotfertilized,corpusluteumofmenstruation

43、degeneratedaftertwoweeksIfoocyteisfertilized,corpusluteumofpregnancy degeneratedafter46monthscorpusalbicans(connectivetissue)SecondaryfollicleCorpusluteumofmenstruationEndocrineinOvaryThecellsofthecainterna andzonagranulosa androgenestrogenthecaluteumcellsestrogen(withgranulosaluteumcells)granulosal

44、uteumcellsprogesteroneHiluscellsandrogenCorpusluteumofpregnancy progesterone,estrogen,relaxinWallmucosaepitheliumsimplecolumnarlaminapropriaathinlayerofC.T. ciliatedcell secretorycellmuscularissmoothmuscle,circular(inner)andlongitudinal(outer)serosa L.C.T.+mesothelium(fibrosa+mesothelium)Oviduct(Fal

45、lopianTube)infundibulum,ampulla,isthmus,uterinepartAmpullainoviductMucosafromampullainoviductIsthmusinoviduct Structureofuterinewallendometriummyometrium perimetrium-epithelium-LPserosamyometriumlaminapropriaUterusepithelium1.EndometriumSimplecolumnarepitheliumSecretorycells+ciliatedcellsLaminapropr

46、iathick,CT,uterineglands,stromacells,richinbloodvessels Theepitheliafromendometrium(SEM)ClassificationofEndometriumStratumfunctionale4/5layerfromthesurfaceofendometrium,periodicchangesunderthestimulationofhormonesfromovarymenstruationDuringthepregnancy,itbecomesthesiteforimplantationandfetalgrowth.S

47、tratumbasale1/5layerjustbeneaththestratumfunctionale,noperiodicchanges,repairedbystratumfunctionale.2.Myometriumthick,consistsofsmoothmusclecells,connectivetissue,bloodvesselsandnerves.Threeill-definedlayers:inside,athincircularlayer,centrally,athickreticularlayer,outside,athincircularlayer3.Perimet

48、riumcoveredbyaperitonealserosa,butcervixfibrosaBloodCirculationinUterus Uterineartery(muscularis) (branches)Basalartery(straightandshort,nutritionforbasallayer) (majorstem) Helicalartery(nutritionforfunctionallayer,affectedbyhormones)Capillary network (superficial layer in the endometrium,affectedby

49、hormones) SmallveinsUterineveinAmodelforbloodvesselsanduterineglandsfromendometriummenstrualcycle Inthesexually-mature,non-pregnantfemalethegenitalorgansundergoperiodically-recurringchanges(28days),whicharecausedbyhormonesofthehypothalamicadenohypophyseal-ovarianaxis.Cyclichistologicalchangesaremost

50、markedintheendometriumofthecorpus,wherethreetypicalphasescanbedistinguishedmenstrualphase1stday4thdayproliferativephase5thday14thdaysecretoryphase15thday28thdayTheCyclicalChangesinUterineEndometrium1.ProliferativePhaseOvary Folliculardevelopmentandgrowth,ovulation,hormone(estrogen)UterineEndometrium

51、 Initially, the uterine glands are short, straight, tubular andfew,buttowardstheendofthephase,theybecomecoiledandtheir cells start to store glycogen. The stroma cells areproliferatedandpackedtightly. Thehelicalarteriesbegintosprout into the growing functional layer. During the late ofproliferative p

52、hase, the endometrium increases in thethicknessto2-3mmorevenmore.ProliferativephaseofuterineendometriumL.M.(E:functionallayer,M:basallayer,G:uterinegland,S:stroma)Theendofproliferativephaseinuterineendometrium(L.M.)2.SecretoryphaseOvarycorpusluteumformed,progesteroneestrogenUterineEndometriumcontinu

53、etoincreaseinthickness,reaching57mm. Theuterineglandsbecomemorecoiledandtheircellsaccumulateglycogen.Duringthatprocess,thenuclei,whichwerelocatedcentrallyatfirst,becomeorientedapically.Thehelicalarteriesalsobecomemoreandmorecoiledandcanreachsurfaceofendometrium.Thelaminapropriaisedemaandstromacellsa

54、refurtherproliferative,becomingthepredecidualcells(roundandlargerinsize,containingglycogenandlipiddroplets).Iffertilizationtakesplace,theendometriumbecomesdecidua.Ifnot,theendometriumenterthemenstrualphase.Secretoryphaseofuterineendometrium(L.M.)Theendofsecretoryphaseinuterineendometrium(L.M.)3.Mens

55、trualPhaseOvarycorpusluteumofmenstruationdegenerating,progesteroneandestrogenUterineendometriumThehormonecausesvasoconstrictionofthehelicalarteriesanduterineglandsstopsecretion,leadingtheischemia,degenerationandnecrosisofthefunctionallayer,thenfunctionallayerissloughed,butthebasallayersuppliedbystra

56、ightarteries,doesnotbecomenecrotic.Whentheestrogenlevelrisesagain,transientvasodilatationcausesbleedingandthesheddingofthenecrotictissuemenstruation.Severaldayslater,thefunctionallayerisregeneratedfromthecellsofthebasallayer.Menstrualphaseofuterineendometrium(L.M.)Amodelforcyclicalchangesinuterineendometrium

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