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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
Gonad development
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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
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:
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
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
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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