醫(yī)學(xué)遺傳與胚胎發(fā)育：7-1Human Embryology-1

——EarlystagesofdevelopmentHumanEmbryologyForeachandeverychild,alsoforcandidatesofmedicaldoctorWheredidIcomefrom

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

period:the28thweekto1stweekafterbirth.TimeofBirth266daysEarlyStagesofDevelopmentinHumanEmbryoItindicatesthetimebetweenbeginningoffertilizationto8thweekendforprimitivehumanbodysetting,includinggameteandfertilization,cleavageandformationofblastocyst,implantation,embryonicdiscformationanddifferentiation,fetalmembraneandplacenta,including:Pre-embryoperiodand

periodofembryogenesis.1.ThepreparationoffertilizationGermcells’developmentandmaturationFertilizationCompositionReproductiveglandtestisGenitalductsepididymis,

vasdeferens,ejaculatoryduct&urethraAccessorysexglandsprostategland,seminalvesicle&bulbourethralglandExternalgenitalorgans

penis&scrotumMaleReproductiveSystemFunctionTestis

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

layers)Sertolicells(only1layer)BasementmembraneTheoutsideofbasementmembranemyoidcell,collagenousfibertoformlimitingmembraneTestisspermatogoniaprimaryspermatocytessecondaryspermatocytesspermatidsspermatozoaSpermatogenicCells1.SpermatogoniumCellisrelativesmallinsize，situatednexttothebasallamina.46xy,2nDNA,mitosisAType(Ad→Ap)→BTypeAd

Type:nucleusshowsoval

shape

anddarkstaining,belongtostemcell

ApType:nucleusshowsoval

shape

andlightstainingB

Type:roundnucleusandroughchromatin→primaryspermatocyte2.PrimarySpermatocyteThelargestcells，severallayersLargeandroundnucleus，darkstaining，roughorgranularchromatin46xy,4nDNAFirstmeioticdivision→secondaryspermatocyte3.SecondarySpermatocyteAdjacentlylocalizedinthelumenofseminiferoustubules,smallinsize,short-livedcellsRoundnucleus，darkstaining23x

or23y,2nDNASecondarymeioticdivision→spermatid4.SpermatidJuxtaluminallocationwithintheseminiferoustubules,distinguishedbytheirsmallinsize,nucleiwithareasofcondensedchromatin(roundnucleitoflatnuclei)Cellsinroundshape→

inelongatedshape23x

or23y,1nDNATransformingto→spermatozoa4.Spermatid

SpermiogenesisanditsprocedureNucleus→flatshapeandcondensed，Golgiapparatus→acrosomalvesicle→acrosomeCentriole→flagellumMitochondriagraduallymovetowardtheflagellumandarrangethemselvesasaspiralaroundthemiddlepiece→sheathofmitochondriaCytoplasm→residualbodies→sheddingSpermiogenesis賀憶培，季穎婕，黃敏，丁之德。精子變形中相關(guān)蛋白的研究進(jìn)展?！秶?guó)際生殖健康/計(jì)劃生育雜志》

2014;

33(6):432-436

基金資助上海交通大學(xué)醫(yī)學(xué)院第七期大學(xué)生科學(xué)創(chuàng)新項(xiàng)目

（2012009）；第七期國(guó)家大學(xué)生科學(xué)創(chuàng)新項(xiàng)目。作者單位

上海交通大學(xué)醫(yī)學(xué)院2011級(jí)臨床醫(yī)學(xué)八年制Spermatogenesis&structureofhumanspermatozoon5.SpermatozoonTadpole-shaped,length≈60μm,

head(5μm)andtail5.SpermatozoonHeadNucleus(DNA)；Acrosome：covered2/3nucleus,containingacrosin

andseveralotherproteolyticenzymes→

Fertilization5.SpermatozoonTailAxoneme(9+2microtubules)—motilityFourpiecesNeck,middlepiece,principalpieceandendpieceNeck:short,ContainingcentrioleMiddlepiece:spermaxoneme,outercondensedfibersheath,mitochondrialsheath—providingenergy5.SpermatozoonTail5.Spermatozoon

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

days)Synchronousdevelopment

1.Spermatogoniaproliferation

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

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

Spermatogonia：ATypeB

TypeA

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

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

Agroupofthecellshavecharacteristicsofsteroidsecretorycell,adjacenttothebloodandlymphaticvessels.StructuresLMRoundedorpolygonalinshape,acentralnucleusandaeosinophiliccytoplasmrichinsmalllipiddroplets

seminiferousepithelium→spermatogenesisT

bloodsecondarysexualcharacteristicslibido(sexualfunction)developmentofgenitalorgansFunction

synthesizeandsecreteandrogen

EMRichinSER,Thecristaeofmitochondriashowtubularinshape,ContaininglipiddropletsMr.ArnoldSchwarzeneggerSeminiferousEpithelium

&TesticularInterstitiaReteTestis,DuctuliEfferentes(EfferentDuctules)andDuctusEpididymisCaput

efferentduct—pseudostratifiedcolumnarepitheliumLumenisirregularinshape,containingtallcolumnarciliatedcellsandshortcolumnarnon-ciliatedcells.Corpus&Cauda

epididymalduct—pseudostratifiedcolumnarepitheliumLumenisregularinshape,containingtallcolumnarciliatedcells(stereocilium)andbasalcells.

Function

spermatozoastorageandmaturation,

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

Caput,CorpusandCaudafromEpididymisDuctuliEfferetes(EfferentDuctules)fromEpididymisMucosapseudostratifiedciliatedcolumnarepithelium

laminapropria:richinelasticfibersplica:longitudinalfoldsMuscularis

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

DeferentDuctAccessorySexGlandsprostateglandseminalvesiclebulbourethralglandSecretionstoform

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

ReprodToxicol2010LiDK,etal.

FertilSteril2010BisphenolAPollutionandMaleInfertilityMendiolaJ,etal.

JAndrol

2011

di(2-ethylhexyl)phthalate(DEPH)DEPHandBPA周婉格，王統(tǒng)菲，周任綜述；丁之德審校。DEHP對(duì)哺乳動(dòng)物生殖系統(tǒng)影響的研究進(jìn)展；《國(guó)際生殖健康/計(jì)劃生育雜志》2013;32(1):50-54李倩,應(yīng)倩綜述；丁之德審校。雙酚A對(duì)哺乳動(dòng)物生殖系統(tǒng)影響的研究進(jìn)展；《國(guó)際生殖健康/計(jì)劃生育雜志》2012;31(6):46-50作者單位:

上海交大醫(yī)學(xué)院09級(jí)臨床醫(yī)學(xué)八年制

基金資助：上海交通大學(xué)醫(yī)學(xué)院第五期大學(xué)生創(chuàng)新項(xiàng)目

（2011025）；第五期上海市大學(xué)生創(chuàng)新訓(xùn)練項(xiàng)目。MaleObesity

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

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

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

Mol

Reprod

Dev

2014;

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

produceoocyte,

synthesizeandsecretefemalesexualhormonesOviduct

transportoocyte,thesiteforfertilization

Uterus

fetusgrowthVaginaandVulva

MammaryglandsbabyfeedingFemaleReproductiveSystemGeneralStructureSurface

a

singlelayerofsquamousorcuboidalcellsTunicaalbuginea

athinlayerofdenseconnectivetissueCortexouterpart,thick,CT,oocytesindifferentstages,reticularfibersandstromacellsMedulla

centralpart,CT,richinbloodvesselsandelasticfibers

aswellasnervesHilus

vesselsandnervereachandleave,CT,hiluscells,androgensecreting,smoothmusclesOvaryAmodelforovarystructureFollicle

oocyte+

follicularcells1.PrimordialFolliclesuperficiallayerofcortex,alargeamountofcells,ball-shapePrimaryoocyte

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

asinglelayerofsquamouscells,smoothsurface,celljunctionsbetweentheprimaryoocyteandfollicularcells，athinlayerofbasalmembraneoutside

Follicle’Development&Maturation

2.GrowingFollicle(1)PrimaryFollicle

primaryoocyteincreaseinsize,50-80μm

follicularcellsasinglelayerofsquamouscells→cuboidalcellsorseverallayers

zonapellucida:betweentheprimaryoocyteandfollicularcells

—sperm-oocyterecognition

thecafolliculi—thecainternaandthecaexternaZonaPellucida

(ZP)

betweentheprimaryoocyteandfollicularcells,ahomogeneouseosinophilicmembraneofglycoprotein①Primaryoocyte

FSH

stimulating,increaseinsize,125-150μm,ZP5μm②Follicularcells

antrumfolliclecontainingfollicularfluid,

composedofsecretoryfluidfromfollicularcellsandpenetratedfluidfrombloodvesselsofthecafolliculi

,cumulusoophorus,coronaradiata,granulosacellstoformzonagranulosa.

（2）SecondaryFollicle

granularcells

primaryoocyteSecondaryFollicle(TEM)3.MatureFollicle(TertiaryFollicleorGraafianFollicle)

Theterminalstageoffolliculardevelopment,thefullsizeof25mm,abulgeonthesurfaceoftheovary(stigma),accumulationoftheliquorfolliculi,enlargedantrum,zonagranulosabecomingprogressivelythinner3.MatureFollicle

Beforethe36-48hrsofovulation，primaryoocytecanfinishthefirstmeiosis，formingsecondaryoocyteand

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

MolReprodDev

2014;81:315-325*CorrespondingAuthorEpigeneticsinGameteandFetusDevelopments李美姿、姜夢(mèng)迪、黃楷綜述；丁之德審校。表觀(guān)遺傳學(xué)與哺乳動(dòng)物配子和胚胎發(fā)生發(fā)育的研究進(jìn)展；《中國(guó)男科學(xué)雜志》2015;29(1):63-66作者單位:

上海交大醫(yī)學(xué)院2012級(jí)臨床醫(yī)學(xué)專(zhuān)業(yè)基金資助：上海交通大學(xué)醫(yī)學(xué)院第八期大學(xué)生創(chuàng)新項(xiàng)目（2014011）

Primaryoocyte(46,XX2nDNA)

firstmeiosisFirstpolarbody+Secondaryoocyte(23,X2nDNA)

metaphaseinsecondarymeiosis

fertilized

unfertilizedsecondarymeiosisfinishSecondarypolarbody+matureoocyteDegeneration

(23,X1nDNA)4.TheSynthesisofEstrogenDuringtheoocytedevelopment,estrogencanbesynthesizedandsecretedbycellsfromboththecagranulosaandthecainterna.Thecellsofthecainterna(LHR)→

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

Estrogen→antrumfolliculiandbloodcirculation↓targetcellsandtissues

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

radiataandtheliquorfolliculiandZP,arereleasedintothepelviccavityandsweptintotheoviductbyitsfimbriatedfunnel.

OvulationAmodelforovulationofmaturefollicleOvaryOocyte

OvulationCorpusLuteum—Formation&DegenerationAfterovulation,therupturedfolliclecollapses,anditsholeisfilledbyahemorrhage.Followingseveraldays,itbecomesacellmasswithyellowcolorunderfreshconditionandsecretsthesteroidhormones.Granulosaluteincells

derivedfromgranulosacells,polygonalshape,increaseinsize,lightstaining,localizedincentralpartofcorpusluteum,secretingprogesteroneandrelaxinThecaluteincells

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

★granulosaluteincells)TheChangesinCorpusLuteumIfoocyteisnotfertilized,corpusluteumofmenstruation

degeneratedaftertwoweeksIfoocyteisfertilized,

corpusluteumofpregnancy

degeneratedafter4～6

months

corpusalbicans(connectivetissue)

SecondaryfollicleCorpusluteumofmenstruationEndocrineinOvaryThecellsofthecainterna

andzonagranulosa

androgen→estrogenthecaluteumcellsestrogen

(withgranulosaluteumcells)granulosaluteumcellsprogesteroneHiluscellsandrogenCorpusluteumofpregnancy

progesterone,estrogen,relaxinWallmucosa

epithelium

simplecolumnar

laminapropriaathinlayerofC.T.

ciliatedcell

secretorycellmuscularis

smoothmuscle,circular(inner)andlongitudinal(outer)serosa

L.C.T.+mesothelium

(fibrosa

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

Structureofuterinewallendometriummyometrium

perimetrium---epithelium---LP—serosamyometriumlaminapropriaUterusepithelium1.EndometriumSimplecolumnarepithelium

Secretorycells

+ciliatedcellsLaminapropria

thick,CT,uterineglands,stromacells,richinbloodvessels

Theepitheliafromendometrium(SEM)

ClassificationofEndometriumStratumfunctionale4/5layerfromthesurfaceofendometrium,periodicchangesunderthestimulationofhormonesfromovary—menstruationDuringthepregnancy,

itbecomesthesiteforimplantationandfetalgrowth.Stratumbasale1/5layerjustbeneaththestratumfunctionale,noperiodicchanges,repairedbystratumfunctionale.2.Myometriumthick,consistsofsmoothmusclecells,connectivetissue,bloodvesselsandnerves.Threeill-definedlayers:inside,athincircularlayer,centrally,athickreticularlayer,outside,athincircularlayer3.Perimetriumcoveredbyaperitonealserosa,butcervix—

fibrosaBloodCirculationinUterus

Uterineartery（muscularis)

(branches)

Basalartery(straightandshort,nutritionforbasallayer)

(majorstem)

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

Smallveins

UterineveinAmodelforbloodvesselsanduterineglandsfromendometriummenstrualcycle

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

1stday～4thdayproliferativephase

5thday～14thdaysecretoryphase

15thday～28thdayTheCyclicalChangesinUterineEndometrium1.ProliferativePhaseOvary

Folliculardevelopmentandgrowth,ovulation,hormone(estrogen)↑UterineEndometrium

Initially,theuterineglandsareshort,straight,tubularandfew,buttowardstheendofthephas