gametogenesis and development of the fertilized ovum · 2018-11-01 · gametogenesis and...

Gametogenesis and Development of the Fertilized Ovum

InaS.Irabon,MD,FPOGS,FPSRM,FPSGEObstetricsandGynecology

ReproductiveEndocrinologyandInfertilityLaparoscopyandHysteroscopy

Todownloadlecturedeck:

References

• CunninghamFG,LevenoKJ,BloomSL,SpongCY,DasheJS,HoffmanBL,CaseyBM,SheffieldJS(eds).William’sObstetrics24thedition;2014;chapter7

• ComprehensiveGynecology7thedition,2017(LoboRA,GershensonDM,LentzGM,ValeaFAeditors);chapter4

outline

• Gametogenesis

• Ovarianfolliculogenesis

• Fertilization

• Blastocystimplantation

• Embryonicperiod

Definitionofterms

• Oogenesis:Thedevelopmentoftheovumfromanoogoniumbymeiosis

• Spermatogenesis:Thedevelopmentofmaturespermfromspermatogoniabymeiosis

• Conceptionalage:Theageoftheconceptusfromfertilization

• Gestationalage:Thestageoftheembryocountingfromthefirstdayofthelastmenstrualperiod.

• Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Hoffman BL, Casey BM, Sheffield JS (eds).William’s Obstetrics 24th

edition; 2014; chapter 7• Comprehensive Gynecology 7th edition, 2017 (Lobo RA, Gershenson DM, Lentz GM, Valea FA editors); chapter 4

• Fertilization:Thepointatwhichonespermatozoonpenetratestheoocyte

• Conceptus:Thefertilizedoocyteanditsderivativesatallstagesofdevelopmentfromfertilizationuntilbirthandincludingallextraembryonicmembranes

• Embryo:Thedevelopmentalstageoftheconceptusafterthedevelopmentoftheprimitivestreakanduntilallmajororgansaredeveloped

Definitionofterms



• Zygote:onecellstageofthefertilizedovumafterpronuclearmembranebreakdownbutbeforethefirstcleavageoccurs

• Morula:Aballofcellscomprisingtheearlyembryothatproducesboththeembryoandtheplacentaandmembranes

• Blastocyst:Thestageoftheconceptusthatfollowsthemorulastage.Itconsistsofafluidfilledcavitysurroundedbytrophoblastswithembryoniccellsatonepole

Definitionofterms



Gametogenesis

• Oogenesis

• Spermatogenesis

Spermatogenesis

• aprocessbywhichprecursorcellstermedspermatogoniaundergoacomplexseriesofdivisionstogiverisetospermatozoa

• Occurswithintheseminiferousepithelium

• Proliferationanddifferentiationofspermatogoniabymitosis

• Primaryspermatocytes(2n)undergo2meioticdivisionstoproducehaploidspermatids(n)

• CunninghamFG,LevenoKJ,BloomSL,SpongCY,DasheJS,HoffmanBL,CaseyBM,SheffieldJS(eds).William’sObstetrics24thedition;2014;chapter7;ComprehensiveGynecology7thedition,2017(LoboRA,GershensonDM,LentzGM,ValeaFAeditors);chapter4

Spermatogenesis

• Approximately72daysarerequiredtoproducematurespermatozoa

• Maturespermatozoa(n)arestoredinthecaudalepididymispriortoejaculation

• Preservationofoptimumspermfunctionduringstoragerequiresadequatetestosteronelevelsincirculationandmaintenanceofnormalscrotaltemperature


Spermatogenesis


OvarianGametogenesis

• Oogenesisistheprocessbywhichfemalegametesdevelopintheovaries

• Unlikeinmales,allprimaryoocytesareproducedduringfetaldevelopment

• Theprecursorstemcellsinfemalesarecalledoogonia(oogonium,sing.)


OvarianGametogenesis(Oogenesis)

• Oogenesisbeginsinfetallifewhentheprimordialgermcells,oroogonia,migratetothegenitalridge(6weeks)

• Thenumberofoogoniaincreasesdramatically:• 2ndmonthAOG:600,000• 10-12thweeksAOG:6-7

million(maximum)


OvarianGametogenesis

(Oogenesis)

• byaprocessofapoptosisandatresiaoftheenvelopingfollicle,thenumberofprimaryoocytesdeclinesfromabout2to4millionatbirthtobecome90%depletedbypuberty.

• byage37:25,000-37,000

• byage50:<1000oocytesremain.

• William’sObstetrics24theditionchapter7;• ComprehensiveGynecology7theditionchapter4

• Theoogoniathenbeginmeioticdivision(primaryoocytes)

• diplotenestageoftheprophase(thegerminalvesicularstage)

• **primaryoocyctesremainindiplotenestageuntilstimulationbygonadotropinsinadulthoodduringthemenstrualcycle.

OvarianGametogenesis(Oogenesis)


OvarianFolliculogenesis

• Theprimaryoocyteissurroundedbyasinglelayerofgranulosacellsinaunitreferredtoastheprimordialfollicle.

• primary(orpreantral)follicles(multiplelayersofgranulosacellssurroundthem)

• **Developmentoffolliclestothisstageappearstoberelativelyindependentofpituitarycontrol

• **occursduringthenonovulatorystagesofchildhood,pregnancy,oralcontraceptiveuse,aswellasduringovulatorycycles.


OvarianFolliculogenesis

• Withformationofanantrum,thefollicle(secondaryorantralfollicle)entersthefinalstagesoffolliculogenesis

• transitionfromintraovarianregulationtoamajorcontrolbythehypothalamic-pituitaryunit.

• ThisrequiresthepresenceofthecharacteristicincreaseinFSHthatoccursintheearlymenstrualcycle.


OocyteMeiosis1stmeioticarrest

2ndmeioticarrest


• Thedevelopmentprocessfromprimaryfollicle(preantralfollicle)tosecondaryorantralfollicle,andtoamaturepreovulatoryfollicletakesabout1yeartocomplete.

• Onlyabout400folliclescompletethisprocess

• themajorityoffolliclesundergoprogrammedcelldeath.


FollicleDevelopment



Oogenesisandthefertilizedovum

Oogonium(2n)

Primaryoocyte(2n)

Firstpolarbody(n) Secondaryoocyte(n)

Secondpolarbody Ovum(n)

(Beforebirth)

MeiosisI

MeiosisII

Duringfetaldevelopment,alltheoogoniadifferentiateintoprimaryoocytes.ThesecellsremainfrozeninPROPHASEIofmeiosis(diplotenestage)à FIRSTMEIOTIC ARREST

Whenthefemalereachespuberty,primaryoocytewillcompletemeiosisItoproducesecondaryoocyte,whichwillremainfrozenatmetaphaseIIofmeiosisà 2NDMEIOTICARREST

Duringfertilization,thesecondaryoocytewillcompletemeiosisIItoproducethematureovum(eggcell)


Follicularphase

• Thefollicularphasecanbesubdividedintothreeperiods:

1. successiverecruitmentofacohortofantralfollicles

2. selectionofadominantfollicle

3. growthoftheselecteddominantfollicle.



RecruitmentofaCohortofAntralFollicles

• FSHprovidesthecriticalsignalfortherecruitmentofacohortofpreantralfollicles(cyclicrecruitment)

• Thisisthemajorsurvivalfactorthatrescuesthefolliclesfromtheirprogrammeddeath(atresia)andallowsthemtostartgrowing,increasinginsizeandbeginningtosynthesizesteroids.



SelectionofaDominantFollicle

ONLYONEIS

SelectionofaDominantFollicle“survivalofthefittest”

• usuallyonlyonefollicle(the“dominantfollicle”)isselectedtocompletegrowthtomaturity.(**otherfolliclesinthecohortbecomeatretic)

• HowwastheDOMINANTfollicleselected??• well-vascularizedthecalayerallowing

abetteraccessofthegonadotropinstotheirtargetreceptors.

• Thisresultsinagreaterlocalestradiolsecretion,whichinturnincreasesthedensityofgonadotropinreceptorsandpromotescellmultiplication.

SelectionofaDominantFollicle

ProductionofEstradiol

“2cell–2g0nadotropintheory”

Thecacellà LHreceptorGranulosacellà FSHreceptor



Dominantfollicle

• Asthedominantfolliclegrows,anantrum(cavity)formsintowhichfollicularfluidaccumulates.

• Thisfluidcontainsseveralsteroids,peptideandproteinhormones,andnutrients.

• increasesinbothfolliclediameterandvolumeparalleltheincreaseinestradiollevelsinblood.

• Atmaturation,thedominantfolliclereachesameandiameterrangeof18-25mm.



TheOvulatoryGonadotropinSurgeandOvulation

• Maturationofthedominantfollicleismarkedbyhighbloodlevelsofestradiol.

• Whenathresholdisreached,estradiolactivatesthepositivefeedbackloopà signalingtothehypothalamusandanteriorpituitaryglandthatthefollicleisreadyforovulationandthatalargegonadotropinsurgeistobereleased

• AsmallbutsignificantincreaseinprogesteroneisalsosecretedbythefolliclebeforetheLHsurge;

• Duringtheovulatorysurge,LHlevelsincrease10-foldoveraperiodof2to3days,whereasFSHlevelsincreaseabout4-fold.

• Thisgonadotropinsurge(LHSURGE)isanabsoluterequirementforthefinalmaturationoftheoocyteandtheinitiationofthefollicularrupture.



LHsurge• TheLHsurgeinitiatesgerminal

vesicle(ornucleus)disruption,andthefullygrownoocyteresumesmeiosis(meioticmaturation).

• Thus,itprogressesfromthediplotenestageofthefirstmeiosistometaphaseIIofthesecondmeioticdivision.

• AstheoocyteentersmetaphaseII,thefirstpolarbodyappears.(Threehaploidpolarbodiesareproducedduringthetwo-stepmeiosisprocess,atovulationandfertilization.)

• Thepolarbodiesgeneratedfromthemeioticeventscontainrelativelylittlecytoplasm,andtheoocyteeventuallydiscardsthem.

• Atovulation,meiosisisarrestedagain(thesecondmeioticarrest).

• Thesecondmeioticdivisionwillonlybecompletedatthetimeoffertilization.

• Theoocyte’sabilitytobefertilizedcoincideswiththecompletionofmeioticmaturation

Ovulation/folliclerupture• Ovulation(folliclerupture)

occursabout32hoursaftertheinitialriseoftheLHsurgeandabout16hoursafteritspeak

• Prostaglandinsthenactlocally—toinducethehyperemiaandedemaseeninthefirsthoursoftheprocessofovulationandwhichresultfromincreasedbloodflowandvascularpermeability.


LutealPhase• Aftertheoocyteisextrudedfromthe

maturedominantfollicle:

1. theamountoffollicularfluidismarkedlyreduced

2. thefollicularwallbecomesconvoluted

3. folliculardiameterandvolumegreatlydecrease.

CORPUSLUTEUM


Corpusluteum

• Likethedominantfollicle,growthanddevelopmentofthecorpusluteumoccurrapidly.

• Vasculargrowthplaysacentralroleinthisprocess.

• Angiogenicfactors,suchasvascularendothelialgrowthfactor(VEGF),arepresentinhighquantityintheforminganddevelopingcorpusluteum.


• Progesteronedominanceduringthelutealphasealsoaffectsthehypothalamicthermoregulatorycenter

• smallincreaseinbasalbodytemperature(BBT)reflectsincreasedprogesteronesecretionduringthelutealphase.

• Thus,thetypicalBBTcurveoftheovulatorymenstrualcycleisbiphasic

EndocrineFactorsandtheCorpusLuteum


What happens if fertilization does not occur?

CorpusLuteumRegression(Luteolysis)

• lifespanofthecorpusluteumislimitedtoaperiodofabout14days.

• thecorpusluteumreachesmaturity8to9daysafterovulation,afterwhichtimelutealcellsstarttodegenerateanditssecretorycapabilitybeginstodecline(corpusalbicans)

• Rapidlyrisingconcentrationsofhumanchorionicgonadotropin[hCG]followingconceptioncanrescuethecorpusluteumandmaintaintheproductionofprogesterone.

TheLuteal-FollicularTransition

• Theendofthelutealphaseischaracterizedbyadramaticdecreaseinprogesterone,estradiol,andinhibinA.

• ThisisaccompaniedbyacharacteristicdivergenceintheFSH:LHratio,nowfavoringaspecificriseinFSH

• TheincreaseintheFSH:LHratioheraldsanewmenstrualcycleandtherecruitmentofanewcohortoffollicles.



What happens if fertilization occurs?

Fertilizationwithinthefirstweek

Stage1:day1-2

Stage2:day2-3

Stage3:day4-5

Stage4:day5-6


AcrosomeReaction

Fertilizedovum:“zygote”(2n)• Undergoesslowcleavagefor3dayswhilestillin

thefallopiantube

• Formationofasolidmulberry-likeballofcells-themorula.Themorulaenterstheuterinecavityabout3daysafter

• Accumulationoffluidbetweenthecellsofthemorulagivesrisetoanearlyblastocyst

• Between3-5daysafterfertilization,theblastuladifferentiatesintothe58cellblastocyst

• 5embryoproducingcellsknownastheinnercellmassand53cellsdestinedtobetrophoblasts


Blastocystimplantation• Sixor7daysafterfertilization,the

embryoimplantstheuterinewall.

• (1)apposition—initialcontactoftheblastocysttotheuterinewall;

• (2)adhesion—increasedphysicalcontactbetweentheblastocystanduterineepithelium;

• (3)invasion—penetrationandinvasionofsyncytiotrophoblastandcytotrophoblastsintotheendometrium,innerthirdofthemyometrium,anduterinevasculature.


Blastocystimplantation• Successfulimplantationrequiresa

receptiveendometriumappropriatelyprimedwithestrogenandprogesteronebythecorpusluteum.

• uterinereceptivityislimitedtodays20to24ofthecycle.

• Iftheblastocystapproachestheendometriumaftercycleday24,thepotentialforadhesionisdiminishedbecauseantiadhesiveglycoproteinsynthesispreventsreceptorinteractions


Blastocystimplantation

• blastocystlooselyadherestotheendometrialepitheliumbyapposition.

• mostcommonlyoccursontheupperposterioruterinewall.


Naegelerule

• add7daystothefirstdayofthelastperiodandsubtract3months,thenadd1year

• Forexample:• LMP:July5,2016• EDD:July5minus3monthsà April5+7days

➔ April12+1yearà April12,2017


Thetrophoblast

• Humanplacentalformationbeginswiththetrophectoderm,whichappearsatthemorulastage.

• trophoblastplaysacriticalpartatthefetal-maternalinterface.

• Itsinvasivenesspromotesimplantation,nutritionalrolefortheconceptus,andisessentialtomaternalphysiologicaladaptationsandtopregnancymaintenance.


Thetrophoblast• Bytheeighthdaypost-

fertilization,afterinitialimplantation,thetrophoblasthasdifferentiatedintoanoutermultinucleatedsyncytium—primitivesyncytiotrophoblast,andaninnerlayerofprimitivemononuclearcells—cytotrophoblasts


Thetrophoblast• Thesyncytiotrophoblastisresponsiblefor

thesynthesisofhumanchorionicgonadotropin(HCG)

• HCGisresponsibleformaintainingthecorpusluteum.

• HCGhasbeendetectedintheperipheralbloodofthemotherasearlyas6daysafterovulation,butitisalwaysseenbyday12.

• Theconcentrationdoublesevery1.2to2days,reachingitshighestpointat7to9weeksofpregnancy.


EmbryonicPeriod

• Theconceptusistermedanembryoatthebeginningofthethirdweekafterovulationandfertilization.

• Primitivechorionicvilliform

• Embryonicperiodlasts8weeks,duringwhichorganogenesistakesplace.

• Theembryonicdisciswelldefined,andmostpregnancyteststhatmeasurehumanchorionicgonadotropinbecomepositivebythistime


• Thebodystalkisnowdifferentiated,andthechorionicsacisapproximately1cmindiameter.

• Duringthethirdweek,fetalbloodvesselsinthechorionicvilliappear.

• Inthefourthweek,acardiovascularsystemhasformed,andthereby,atruecirculationisestablishedbothwithintheembryoandbetweentheembryoandthechorionicvilli.

• Partitioningoftheprimitiveheartbeginsinthemiddleofthefourthweek.Armandlegbudsarepresent,andtheamnionisbeginningtounsheathethebodystalk,whichthereafterbecomestheumbilicalcord.

EmbryonicPeriod


Humansexdifferentiation

• Genetic sex is determined at the time of conception. • Presence of a Y chromosome is necessary for the development of

the testes • primary determinant is the SRY (testes determining factor) gene located

on the short arm of the Y chromosome • testes responsible for:

1. organization of the sexual duct system into a male configuration 2. suppression of the paramesonephric (Mullerian) system

In the absence of a Y chromosome or in the absence of a gonad, development will be female in nature


outline

• Gametogenesis

• Ovarianfolliculogenesis

• Fertilization

• Blastocystimplantation

• Embryonicperiod

Thank You!

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gametogenesis and development of the fertilized ovum · 2018-11-01 · gametogenesis and...

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