Development of the Reproductive System

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Citation: TheDevelopingHuman:clinicallyorientedembryology9th ed.KeithL.
Moore,T.V.N.Persaud,MarkG.Torchia.Philadelphia,PA:Saunders,2011.
Chapter12 UrogenitalSystem

Citation: Larsen'shumanembryology4thed.Schoenwolf,GaryC;Larsen,
WilliamJ,(WilliamJames).Philadelphia,PA :Elsevier/ChurchillLivingstone,
c2009.
Chapter15 DevelopmentoftheUrogenitalSystem

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 Lecture overview

Sex determination

Embryonic origins of the reproductive system

Gonad development

Development of the reproductive tract

Development of the external genitalia

Development of secondary sex characteristics

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 Sex Determination
4partstosexualdevelopmentthatoccursinsequence:

1.Geneticsex
chromosomalcomposition:XXorXY
determinedatconception

2.Gonaddevelopment
Developmentoftestesorovaries
Definedduringembryonicdevelopment

3.Developmentofthesexspecificinternalductsandexternalgenitalia
Hormonedependent
Definedduringfetaldevelopment

4.Secondarysexcharacteristics
Definedatpuberty

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 Timelineofsexualdifferentiationin
humans

Schoenwolf: Larsen's Human Embryology, 4th ed.

Copyright 2008 5
 Embryonic development:
Primordial
GermCells

Page342
S.F.Gilbert
DevelopmentalBiology
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5thedition
Intermediate mesoderm

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Gonads begin as a bulge on the surface of the mesonephric region
of the urogenital ridge called the genital ridge

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Adrenalglandsdevelopadjacenttothegonadsintheurogenitalridge

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Originofthecelllineages

Coelomic epithelium
proliferation

Mesonephric contribution

Primordialgermcells
migration

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Originoftheprimordialgermcellsattheposteriorendoftheprimitivestreakatthe
junctionofyolksacandthehindgut

Primordialgermcells(PGCs)arethought
tobethefirstpopulationofcellsto
migratethroughtheprimitivestreakin
earlygastrulation(week3)

latermigrateintothegenitalridge(germinal
ridge)inearlyembryonicdevelopment

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 Migration of the primordial germ cells

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http://php.med.unsw.edu.au/embryology/images/2/26/Primordial_germ_cell_002.mp4
Beforesexualdifferentiationthedevelopinghumanhasarelatively
undifferentiatedgonadalprimordium andtwoadjacentductstructures

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 Gonad Development
Bipotential organs the indifferent gonad

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(From:Mousedevelopment,Ch.SexDeterminationanddifferentiation,SwainandLovellBadge)
 Gonad Development
Bipotential tissues

Male: Female:

Testes(seminiferous tubules) Ovary

Gonad

Ductalsystemsin
Epididymus Infundibulum
mesonephros:
Vasdeferens Oviduct
Wolffian duct
Ejaculatoryductandinputs: Ampulla
Mullerian duct
Uturus
Cervix
UpperVagina

Penis LowerVagina
Genitaltubercle
Urethra Clitoris

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 Gonad Development
Bipotential cells

Sertoli cells Granulosa cells

Somaticgonadcells
Leydig cells Thecacells
Spermatogonia Germcells Oogonia

Peritubular Mesonephric cells

Myoid cells

Celltypesinthegonad
Somatic
Supportingcells becausetheyendupsupportingthegermcellsinbothtestisandovary
Steroidsecretingcelllineage giverisetosteroidhormonesecretingcells
Peritubular myoid cells
Vascularendothelialcells

Primordialgermcells
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Gonadal differentiation into testis or ovary

Testis

Ovary

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(Adapted from Ross and Capel, 2005)
 Early mouse gonadal differentiation

Embryonictestis Embryonicovary

Leydigcells
Sertoli cells
Mesonephros Germcells

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What is the genetic mechanism for sex determination?
X/autosome ratio?
Dominant Y chromosome gene?

Testis

Ovary

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(Adapted from Ross and Capel, 2005)
 Sry, the male sex determining gene
SRY encodesa204aminoacidprotein(TDF)thatisamemberoftheHMG(Highmobilitygroup)boxclassofDNA
bindingproteins.TranscriptionfactorsbindtospecificsitesofDNAandregulatesthetranscription(expression)of
othergenes.

Ychromosome

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Xchromosome
155millionbasepairs,containsabout5%ofthehaploidgenomeand
encodeshousekeepingandspecializedfunctions.GenessuchasWnt
4andDAX1necessaryforinitiationoffemalepathwayovary
development.
Anearlydiscovery(1961)wasthatinordertohavecorrectlevelsofX
chromosomegene/proteinexpression(genedosage),femalesmust
"inactivate"asinglecopyoftheXchromosomeineachandeverycell.

TheinitiatoroftheXinactivationprocesswasdiscovered(1991)tobe
regulatedbyaregionontheinactivatingXchromosomeencodinganX
inactivespecifictranscript(XIST),thatactsasRNAanddoesnot
encodeaprotein.

Xinactivationoccursrandomlythroughouttheembryo,generatinga
mosaicofmaternalandpaternallyderivedXchromosomeactivityinall
tissuesandorgans.Thiscanbeseeninthefurcolour oftortoiseshell
cats

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TheexpressionofSry dominantlyactivatestestisdevelopment
IntheabsenceofSry,thedefaultprogramofovarydevelopmentinitiates

SRY NOSRY
EffectofSry expressiononthecelllineageswithintheindifferentgonad

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Testisandovarydevelopmentmovies

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 Adult testis and ovary

http://php.med.unsw.edu.au/embryology/images/7/7f/Testis_001.mp4
http://php.med.unsw.edu.au/embryology/images/7/7b/Ovary_001.mp4

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 Development of Reproductive Tract

Sertoli cells produce anti-Mllerian hormone:

Mllerian duct regression

Leydig cells produce testosterone: Wolffian duct

development into rete testis, epidydimus and vas
deferens.

In absence of these hormones: loss of Wolffian

duct, Mllerian duct develops female reproductive
tract: oviduct and uterus

http://php.med.unsw.edu.au/embryology/images/7/7f/Testis_001.mp4
http://php.med.unsw.edu.au/embryology/images/7/7b/Ovary_001.mp4
http://php.med.unsw.edu.au/embryology/images/1/12/Uterus_001.mp4

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Femalereproductivetractdevelopment

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Developmentofexternalgenitalia indifferentstage

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Formationoftheexternalgenitaliain
malesandfemales.A,Theexternal
genitaliaformfromapairof
labioscrotal folds,apairofurogenital
folds,andananteriorgenital
tubercle.Maleandfemalegenitalia
aremorphologically
indistinguishableatthisstage.B,In
males,theurogenitalfoldsfuseand
thegenitaltubercleelongatesto
formtheshaftandglansofthe
penis.Fusionoftheurethralfolds
enclosesthephallicportionofthe
urogenitalsinustoformthepenile
urethra.Thedistalurethraisformed
bycanalizationofasolidendodermal
extensionoftheurethralplateinto
theglans.Thelabioscrotal foldsfuse
toformthescrotum.C,Infemales,
thegenitaltuberclebendsinferiorly
toformtheclitoris,andthe
urogenitalfoldsremainseparatedto
formthelabiaminora.The
labioscrotal foldsformthelabia
majora

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Development of the external genitalia

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Descentofthetestes startsweek26

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Development of secondary sex characteristics
Puberty

Activationofspermproduction Activationofmenstrualcycle
Masculinization Feminization 33
Hairgrowth Hairgrowth
Disorders of sexual development

Sexreversal
Hermaphroditism
ambiguousexternalgenitalia
Truehermaphrodite bothovarianandtesticulartissues
Generally46,XX(crossingover,XwithshortarmofY)
Ovotestes formation medullaandcortexdevelopment
Malepseudohermaphroditism 46,XY
Externalgenitaliaandductsareintersex
InadequatetestosteroneorabnormalAMHproduction
Femalepseudohermaphroditism 46,XX
Overproductionofandrogens
Masculinizationofgenitalia clitoralhypertrophy
Androgeninsensitivitysyndrome
(Testicularfeminizationsyndrome) 46,XY
femaleinallwaysbutwithtestis
resultsfromandrogenreceptordefects
Hypospadiasandcryptorchidism
http://php.med.unsw.edu.au/embryology/index.php?title=Development_Animation__Testis_Descent

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