医学遗传与胚胎发育 Chapter 7.1 Human Embryology-1

——EarlystagesofdevelopmentHumanEmbryology1Foreachandeverychild,alsoforcandidatesofmedicaldoctor2WheredidIcomefrom

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?17Humanembryologyissciencefocusedontheresearchesofontogenesis,developmentanditsvariationforhumanbody.ConceptInclusionsHumanEmbryologyPeriodoffertilizedovumorzygotetoblastocystFertilizationbeginningtothesecondweekend:includingfertilization,cleavage,blastocystformationandbeginningofimplantationPeriodofembryogenesisThethirdweektoeighthweekends:embryonicdiscformation,andprimordiaofprincipalorgansestablishmentandprimitivehumanbodysettingFetalperiodTheninthweektoparturitionPerinatal

period:the28thweekto1stweekafterbirth.TimeofBirth266days18EarlyStagesofDevelopmentinHumanEmbryoItindicatesthetimebetweenbeginningoffertilizationto8thweekendforprimitivehumanbodysetting,includinggameteandfertilization,cleavageandformationofblastocyst,implantation,embryonicdiscformationanddifferentiation,fetalmembraneandplacenta,including:Pre-embryoperiodand

periodofembryogenesis.191.ThepreparationoffertilizationGermcells’developmentandmaturationFertilization20CompositionReproductiveglandtestisGenitalductsepididymis,

vasdeferens,ejaculatoryduct&urethraAccessorysexglandsprostategland,seminalvesicle&bulbourethralglandExternalgenitalorgans

penis&scrotumMaleReproductiveSystem21FunctionTestis

producespermatozoa&secreteandrogenReproductivetractspermmaturation,nutrition,storage&transportationAccessoryglandsThesecretionstoformseminalplasma22SeminiferousTubulesSeminiferousepitheliumSpermatogeniccells(5-8

layers)Sertolicells(only1layer)BasementmembraneTheoutsideofbasementmembranemyoidcell,collagenousfibertoformlimitingmembraneTestis23spermatogoniaprimaryspermatocytessecondaryspermatocytesspermatidsspermatozoaSpermatogenicCells241.SpermatogoniumCellisrelativesmallinsize，situatednexttothebasallamina.46xy,2nDNA,mitosisAType(Ad→Ap)→BTypeAd

Type:nucleusshowsoval

shape

anddarkstaining,belongtostemcell

ApType:nucleusshowsoval

shape

andlightstainingB

Type:roundnucleusandroughchromatin→primaryspermatocyte252.PrimarySpermatocyteThelargestcells，severallayersLargeandroundnucleus，darkstaining，roughorgranularchromatin46xy,4nDNAFirstmeioticdivision→secondaryspermatocyte263.SecondarySpermatocyteAdjacentlylocalizedinthelumenofseminiferoustubules,smallinsize,short-livedcellsRoundnucleus，darkstaining23x

or23y,2nDNASecondarymeioticdivision→spermatid274.SpermatidJuxtaluminallocationwithintheseminiferoustubules,distinguishedbytheirsmallinsize,nucleiwithareasofcondensedchromatin(roundnucleitoflatnuclei)Cellsinroundshape→

inelongatedshape23x

or23y,1nDNATransformingto→spermatozoa284.Spermatid

SpermiogenesisanditsprocedureNucleus→flatshapeandcondensed，Golgiapparatus→acrosomalvesicle→acrosomeCentriole→flagellumMitochondriagraduallymovetowardtheflagellumandarrangethemselvesasaspiralaroundthemiddlepiece→sheathofmitochondriaCytoplasm→residualbodies→shedding29Spermiogenesis贺忆培，季颖婕，黄敏，丁之德。精子变形中相关蛋白的研究进展。《国际生殖健康/计划生育杂志》

2014;

33(6):432-436

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

（2012009）；第七期国家大学生科学创新项目。作者单位

上海交通大学医学院2011级临床医学八年制30Spermatogenesis&structureofhumanspermatozoon315.SpermatozoonTadpole-shaped,length≈60μm,

head(5μm)andtail325.SpermatozoonHeadNucleus(DNA)；Acrosome：covered2/3nucleus,containingacrosin

andseveralotherproteolyticenzymes→

Fertilization335.SpermatozoonTailAxoneme(9+2microtubules)—motilityFourpiecesNeck,middlepiece,principalpieceandendpiece34Neck:short,ContainingcentrioleMiddlepiece:spermaxoneme,outercondensedfibersheath,mitochondrialsheath—providingenergy5.SpermatozoonTail355.Spermatozoon

TailPrincipalpiece:length45μm,spermaxoneme,outercondensedfibersheathEndpiece:spermaxoneme36SpermatogenesisDefinitionSpermatogonia→spermatozoa(64

days)Synchronousdevelopment

371.Spermatogoniaproliferation

MitosisAd→Ap→B→primaryspermatocyte(46XY,4nDNA)2.SpermatocytemeiosisⅠ→23X/23Y,2nDNAⅡ→23X/23Y,1nDNA3.Spermatidtransformation(spermiogenesis)

NochangingbothinDNAandchromosome→spermatozoa(23X/23Y,1nDNA)Spermatogenesisinthreeperiods38Spermatogenesis39SpermatogenicCells

Spermatogonia：ATypeB

TypeA

TypedifferentiationMitosisPrimarySpermatocytes:46XYSecondarySpermatocytes:23X/23YSpermatid:23X/23YSpermatozoa:23X/23YSpermiogenesisSpermatogenesis40SertoliCellsMorphologicalStructureLMElongatedpyramidalcells,partiallyenvelopspermatogeniccells.Cellsadheretothebasallamina,whiletheirapicalendsfrequentlyextendintothelumenoftheseminiferoustubule.Cytoplasmappearspoorlydefined.Nucleusistriangleorirregular,andpalestainingandnucleolusisobvious.EMOrganellesarewelldevelopedincludingRER,SER,Mitochondria,Golgiapparatus,lysosome,microtubuleµfilament.Tightjunctions

→extratubularcompartmentandintratubular(adluminal)compartment.41FunctionSupport,protection,andnutritionalregulationofdevelopingspermatozoa,Phagocytosis:residualbodies,SynthesizeandsecreteInhibitin,Secretetesticularfluidtotransportspermatozoa,Secreteandrogen-bindingprotein(ABP)→highconcentrationofandrogenwithinseminiferoustubules→facilitatethespermatogenesisBuilduptheblood-testisbarriertoprotectthedevelopingspermcellsfromimmunologicattack42Leydig(Interstitial)CellsLocalization

Agroupofthecellshavecharacteristicsofsteroidsecretorycell,adjacenttothebloodandlymphaticvessels.StructuresLMRoundedorpolygonalinshape,acentralnucleusandaeosinophiliccytoplasmrichinsmalllipiddroplets43

seminiferousepithelium→spermatogenesisT

bloodsecondarysexualcharacteristicslibido(sexualfunction)developmentofgenitalorgansFunction

synthesizeandsecreteandrogen

EMRichinSER,Thecristaeofmitochondriashowtubularinshape,Containinglipiddroplets44Mr.ArnoldSchwarzenegger45SeminiferousEpithelium

&TesticularInterstitia46ReteTestis,DuctuliEfferentes(EfferentDuctules)andDuctusEpididymis47Caput

efferentduct—pseudostratifiedcolumnarepitheliumLumenisirregularinshape,containingtallcolumnarciliatedcellsandshortcolumnarnon-ciliatedcells.Corpus&Cauda

epididymalduct—pseudostratifiedcolumnarepitheliumLumenisregularinshape,containingtallcolumnarciliatedcells(stereocilium)andbasalcells.

Function

spermatozoastorageandmaturation,

synthesizeandsecretebioactivemolecules,e.g.carnitine,glycerophosphorylcholine,sialicacidandtestosterone.Epididymis

48Caput,CorpusandCaudafromEpididymis49DuctuliEfferetes(EfferentDuctules)fromEpididymis50Mucosapseudostratifiedciliatedcolumnarepithelium

laminapropria:richinelasticfibersplica:longitudinalfoldsMuscularis

smoothmuscle,thick,innerlongitudinal,middlecircular,outerlongitudinalAdventitiaC.T.

DeferentDuct51AccessorySexGlandsprostateglandseminalvesiclebulbourethralglandSecretionstoform

seminalplasma52Composedbyspermatozoaandseminalplasma,milkycolor,pH≥7.2Normalvolume:1.4~1.7mL/perejaculation，≥15M/mL,alivesperm≥58%，spermmotility≥40%，forwardmotility≥32%,normalmorphologicalsperm≥4%(WHO5th)Ifthespermamountandmotilitydecline,andabnormalmorphologicalspermincreaseorelementsinseminalplasmachangesleadingtomaleinfertilitySemen53PollutionandMaleInfertilityMeekerJD,etal.

ReprodToxicol2010LiDK,etal.

FertilSteril2010BisphenolA54PollutionandMaleInfertilityMendiolaJ,etal.

JAndrol

2011

di(2-ethylhexyl)phthalate(DEPH)55DEPHandBPA周婉格，王统菲，周任综述；丁之德审校。DEHP对哺乳动物生殖系统影响的研究进展；《国际生殖健康/计划生育杂志》2013;32(1):50-54李倩,应倩综述；丁之德审校。双酚A对哺乳动物生殖系统影响的研究进展；《国际生殖健康/计划生育杂志》2012;31(6):46-50作者单位:

上海交大医学院09级临床医学八年制

基金资助：上海交通大学医学院第五期大学生创新项目

（2011025）；第五期上海市大学生创新训练项目。56MaleObesity

andInfertilityYueLiu,YiGuo…ZhideDing*.Proteomicpatternchangesassociatedwithobesity-inducedathenozoospermia.Andrology

2015;3(2):247-59*Correspondingauthor57YueLiu,

WenzhenZhao,…ZhideDing*.Palmitoyl-ProteinThioesterase1(PPT1):AnObesity-InducedRatTesticularMarkerofReducedFertility.

Mol

Reprod

Dev

2014;

81:55-65*CorrespondingauthorObesityandMaleInfertility58ObesityandMaleInfertilityFanY,…DingZ*.Diet-inducedobesityinmaleC57BL/6micedecreasesfertilityasaconsequenceofdisruptedblood-testisbarrier.PLoSOne2015;10(4):e0120775.*Correspondingauthor59MaleFertilityTheyoungestfatherTheoldestfather60MaleContraceptivePills(2012)61CompositionandFunctionOvary

produceoocyte,

synthesizeandsecretefemalesexualhormonesOviduct

transportoocyte,thesiteforfertilization

Uterus

fetusgrowthVaginaandVulva

MammaryglandsbabyfeedingFemaleReproductiveSystem62GeneralStructureSurface

a

singlelayerofsquamousorcuboidalcellsTunicaalbuginea

athinlayerofdenseconnectivetissueCortexouterpart,thick,CT,oocytesindifferentstages,reticularfibersandstromacellsMedulla

centralpart,CT,richinbloodvesselsandelasticfibers

aswellasnervesHilus

vesselsandnervereachandleave,CT,hiluscells,androgensecreting,smoothmusclesOvary63Amodelforovarystructure64Follicle

oocyte+

follicularcells1.PrimordialFolliclesuperficiallayerofcortex,alargeamountofcells,ball-shapePrimaryoocyte

resultsofmitosisofoogoniumandenteringintothephaseoffirstmeiosis,andstopinthestageofprophase,30µmindiameter,cellsinroundshape,lightstaining,prominentnucleolus,eosinophiliccytoplasmcontainingcorticaloocytegranulesFollicularcells

asinglelayerofsquamouscells,smoothsurface,celljunctionsbetweentheprimaryoocyteandfollicularcells，athinlayerofbasalmembraneoutside

Follicle’Development&Maturation65

2.GrowingFollicle(1)PrimaryFollicle

primaryoocyteincreaseinsize,50-80μm

follicularcellsasinglelayerofsquamouscells→cuboidalcellsorseverallayers

zonapellucida:betweentheprimaryoocyteandfollicularcells

—sperm-oocyterecognition

thecafolliculi—thecainternaandthecaexterna66ZonaPellucida

(ZP)

betweentheprimaryoocyteandfollicularcells,ahomogeneouseosinophilicmembraneofglycoprotein67①Primaryoocyte

FSH

stimulating,increaseinsize,125-150μm,ZP5μm②Follicularcells

antrumfolliclecontainingfollicularfluid,

composedofsecretoryfluidfromfollicularcellsandpenetratedfluidfrombloodvesselsofthecafolliculi

,cumulusoophorus,coronaradiata,granulosacellstoformzonagranulosa.

（2）SecondaryFollicle68

granularcells

primaryoocyteSecondaryFollicle(TEM)693.MatureFollicle(TertiaryFollicleorGraafianFollicle)

Theterminalstageoffolliculardevelopment,thefullsizeof25mm,abulgeonthesurfaceoftheovary(stigma),accumulationoftheliquorfolliculi,enlargedantrum,zonagranulosabecomingprogressivelythinner703.MatureFollicle

Beforethe36-48hrsofovulation，primaryoocytecanfinishthefirstmeiosis，formingsecondaryoocyteand

thefirstpolarbody,localizedinperivitellinespace(betweenthesecondaryoocyteandZP).Thechromosomeisdividedintohalfforeach(23,X).Then,secondaryoocyteimmediatelyenterthesecondarymeiosisandstopinthemetaphase.71ERp57andOocyteMaturationYueLiu,YeminZhu,XiaohuiWu,…ZhideDing*.IncreasedExpressionofERp57inRatOocytesDuringMeioticMaturationIsAssociatedWithSperm-EggFusion.

MolReprodDev

2014;81:315-325*CorrespondingAuthor72EpigeneticsinGameteandFetusDevelopments李美姿、姜梦迪、黄楷综述；丁之德审校。表观遗传学与哺乳动物配子和胚胎发生发育的研究进展；《中国男科学杂志》2015;29(1):63-66作者单位:

上海交大医学院2012级临床医学专业基金资助：上海交通大学医学院第八期大学生创新项目（2014011）73

Primaryoocyte(46,XX2nDNA)

firstmeiosisFirstpolarbody+Secondaryoocyte(23,X2nDNA)

metaphaseinsecondarymeiosis

fertilized

unfertilizedsecondarymeiosisfinishSecondarypolarbody+matureoocyteDegeneration

(23,X1nDNA)744.TheSynthesisofEstrogenDuringtheoocytedevelopment,estrogencanbesynthesizedandsecretedbycellsfromboththecagranulosaandthecainterna.Thecellsofthecainterna(LHR)→

takecholesterol(blood)，synthesizeAndrogen(aromatase)→granulosacells(FSHR&LHR)→

Estrogen→antrumfolliculiandbloodcirculation↓targetcellsandtissues75

Fourteendaysbeforetheexpectedonsetofthenextmenstruation,theserumlevelofluteinizinghormone(LH)reachapeak.Enzymesofthefollicularfluidleadtoaruptureofthethinfollicularwall,andthesecondaryoocyte,withitscorona

radiataandtheliquorfolliculiandZP,arereleasedintothepelviccavityandsweptintotheoviductbyitsfimbriatedfunnel.

Ovulation76Amodelforovulationofmaturefollicle77OvaryOocyte

Ovulation78CorpusLuteum—Formation&DegenerationAfterovulation,therupturedfolliclecollapses,anditsholeisfilledbyahemorrhage.Followingseveraldays,itbecomesacellmasswithyellowcolorunderfreshconditionandsecretsthesteroidhormones.79Granulosaluteincells

derivedfromgranulosacells,polygonalshape,increaseinsize,lightstaining,localizedincentralpartofcorpusluteum,secretingprogesteroneandrelaxinThecaluteincells

derivedfromthecellsofthecainterna,smallinsize,darkstaining,localizedinperipheralpartofcorpusluteum,secretingestrogen(togetherwithgranulosaluteincells)80CorpusLuteumL.M.（※thecaluteincells

★granulosaluteincells)81TheChangesinCorpusLuteumIfoocyteisnotfertilized,corpusluteumofmenstruation

degeneratedaftertwoweeksIfoocyteisfertilized,

corpusluteumofpregnancy

degeneratedafter4～6

months

corpusalbicans(connectivetissue)

82SecondaryfollicleCorpusluteumofmenstruationEndocrineinOvaryThecellsofthecainterna

andzonagranulosa

androgen→estrogenthecaluteumcellsestrogen

(withgranulosaluteumcells)granulosaluteumcellsprogesteroneHiluscellsandrogenCorpusluteumofpregnancy

progesterone,estrogen,relaxin83Wallmucosa

epithelium

simplecolumnar

laminapropriaathinlayerofC.T.

ciliatedcell

secretorycellmuscularis

smoothmuscle,circular(inner)andlongitudinal(outer)serosa

L.C.T.+mesothelium

(fibrosa

+mesothelium)Oviduct(FallopianTube)infundibulum,ampulla,isthmus,uterinepart84Ampullainoviduct85Mucosafromampullainoviduct86Isthmusinoviduct87

Structureofuterinewallendometriummyometrium

perimetrium---epithelium---LP—serosamyometriumlaminapropriaUterusepithelium881.EndometriumSimplecolumnarepithelium

Secretorycells

+ciliatedcellsLaminapropria

thick,CT,uterineglands,stromacells,richinbloodvessels89

Theepitheliafromendometrium(SEM)90

ClassificationofEndometriumStratumfunctionale4/5layerfromthesurfaceofendometrium,periodicchangesunderthestimulationofhormonesfromovary—menstruationDuringthepregnancy,

itbecomesthesiteforimplantationandfetalgrowth.Stratumbasale1/5layerjustbeneaththestratumfunctionale,noperiodicchanges,repairedbystratumfunctionale.912.Myometriumthick,consistsofsmoothmusclecells,connectivetissue,bloodvesselsandnerves.Threeill-definedlayers:inside,athincircularlayer,centrally,athickreticularlayer,outside,athincircularlayer3.Perimetriumcoveredbyaperitonealserosa,butcervix—

fibrosa92BloodCirculationinUterus

Uterineartery（muscularis)

(branches)

Basalartery(straightandshort,nutritionforbasallayer)

(majorstem)

Helicalartery(nutritionforfunctionallayer,affectedbyhormones)Capillarynetwork(superficiallayerintheendometrium,affectedbyhormones)

Smallveins

Uterinevein93Amodelforbloodvesselsanduterineglandsfromendometrium94menstrualcycle

Inthesexually-mature,non-pregnantfemalethegenitalorgansundergoperiodically-recurringchanges(28days),whicharecausedbyhormonesofthehypothalamic–adenohypophyseal-ovarianaxis.Cyclichistologicalchangesaremostmarkedintheendometriumofthecorpus,wherethreetypicalphasescanbedistinguishedmenstrualphase

1stday～4thdayproliferativephase

5thday～14thdaysecretoryphase

15thday～28thdayTheCyclicalChangesinUterineEndometrium951.ProliferativePhaseOvary

Folliculardevelopmentandgrowth,ovulation,hormone(estrogen)↑UterineEndometrium

Initially,theuterineglandsareshort,straight,tubularandfew,buttowardstheendofth