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Development of the Reproductive System
DrAnnemiekBeverdam– SchoolofMedicalSciences,UNSWWallaceWurth BuildingRoom234– [email protected]
Resources:http://php.med.unsw.edu.au/embryology/
Larsen’s Human EmbryologyThe Developing Human: Clinically Oriented Embryology
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Lecture overview
DrAnnemiekBeverdam– SchoolofMedicalSciences,UNSWWallaceWurth BuildingRoom234– [email protected]
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
Disorders of sexual development
DrAnnemiekBeverdam– SchoolofMedicalSciences,UNSWWallaceWurth BuildingRoom234– [email protected]
Resources:http://php.med.unsw.edu.au/embryology/
Larsen’s Human EmbryologyThe Developing Human: Clinically Oriented Embryology
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Threefactorsthatdeterminegenderphenotype:
1.Geneticsex- chromosomalcomposition:XXorXY- determinedatconception
2.Gonadandurogenitaltractdevelopment- Developmentoftestesorovaries- Definedduringembryonicdevelopment
3.Developmentofsecondarysexcharacteristics- Hormonedependent- Definedduringpuberty
Sex Determination
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End product gastrulation:Trilaminar embryo
Ectoderm (Neural crest)brain, spinal cord, eyes, peripheral nervous system
epidermis of skin and associated structures, melanocytes, cranial connective tissues (dermis)
Mesodermmusculo-skeletal system, limbs
connective tissue of skin and organsurogenital system, heart, blood cells
Endodermepithelial linings of gastrointestinal and respiratory tracts
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Embryonic tissues contributing to development of the reproductive system
IntermediateMesodermCoelomic EpitheliumPrimordialGermCells
Week4embryo
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EarlyMesodermDevelopment
1 23 4
NeuralTube
1:notochord2:paraxialmesoderm3:intermediatemesoderm4:lateralplatemesoderm
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IntermediateMesodermSegmentedandunsegmentedintermediatemesoderm
MesonephricductUrogenitalsinus
MesonephrictubulesUretericbuds
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IntermediateMesoderm3nephricsystems:- Pronephros:regress- Mesonephros:reproductivesystem,andcollectingductandtubulesofthekidney- Metanephros:nephronsofthekidney
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Coelomic epithelium
Lateralplatemesodermdevelopsinto:- Splanchnic/visceralmesoderm- Somatic/parietalmesoderm
Intraembryoniccoelom:3cavities:- Pericard- Pleural- Peritoneum
Coelomic epithelium
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Gonad developmentPrimordial Germ Cells
http://php.med.unsw.edu.au/embryology/images/2/26/Primordial_germ_cell_002.mp4
PGCsariseduringgastrulationPGCsareinitiallysetapartinhindgut/yolksac/allantoisLaterthePGCsmigrateintothegenitalridgesthroughthehindgutintothegenitalridges
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Gonad developmentPrimordial Germ Cells
http://php.med.unsw.edu.au/embryology/images/2/26/Primordial_germ_cell_002.mp4
PGCsariseduringgastrulationPGCsareinitiallysetapartinhindgut/yolksac/allantoisLaterthePGCsmigrateintothegenitalridgesthroughthehindgutintothegenitalridges
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Intermediatemesodermgivesrisetourogenitalsystem:
Gonad development
Ductalsystemdevelopswithinintermediatemesoderm
Threeregionswithinintermediatemesoderm:1.Pronephros:transient2.Mesonephros:
- formsmesonephric (Wolffian)duct- functionalembryonickidney- formsgonads
3.Metanephros:- ductformsuretericbud- formsadultkidney
Mesonephros iscoveredbycoelomic epithelium
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Gonad development
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�(From:Mousedevelopment,Ch.SexDeterminationanddifferentiation,SwainandLovell-Badge)
�
Gonad DevelopmentBipotential organs
GenitalRidgesSomaticgonadcellsGermcellsWolffian/MesonephricDuctMullerian duct/Paramesonephricduct
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Male:
Testes
EpididymusVasdeferensSeminalvesicle
Ejaculatoryductandinputs:
PenisUrethra
Gonad
Ductalsystemsinmesonephros:Wolffian ductMullerian duct
Genitaltubercle
Female:
Ovary
InfundibulumOviductAmpullaUterusCervix
UpperVagina
LowerVaginaClitoris
Gonad DevelopmentBipotential tissues
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Gonad DevelopmentBipotential gonadal cells
Somaticgonadcells:- Supportingcells
- Steroid-producingcellsSertoli cellsLeydig cells
Granulosa cellsThecacells
PrimordialgermcellsSpermatogonia Oogonia
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��
(Adapted from Ross and Capel, 2005)
Gonad Development
SomaticgonadcellsinXYgonad:Sertoli cellsfirst,thenfetalLeydig cellsFetalLeydig cellsafterbirthreplacedbyadultLeydig cells
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http://php.med.unsw.edu.au/embryology/images/7/7f/Testis_001.mp4http://php.med.unsw.edu.au/embryology/images/7/7b/Ovary_001.mp4
Gonad Development
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Gonad Development
Leydigcells
Sertoli cells
GermcellsMesonephros
Embryonictestis Embryonicovary
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��
(Adapted from Ross and Capel, 2005)
?
Gonad DevelopmentSex determination
SomaticgonadcellsinXYgonad:Sertoli cellsfirst,thenfetalLeydig cellsFetalLeydig cellsafterbirthreplacedbyadultLeydig cells
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Sry, the male sex determining gene
Ychromosome
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Sry is transiently expressed in Sertoli Cells and induces SOX9 expression
Sry expressioninXYgenitalridges
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Sry, the male sex determining gene
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Female:
Ovary
Mullerian Duct:Infundibulum
OviductAmpullaUterusCervix
UpperVagina
Male:
Testes
Wollfian Duct:EpididymusVasdeferensSeminalvesicleEjaculatoryduct
Urethra
Development of Reproductive Tract
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Development of Reproductive Tract
• Sertoli cells produce anti-Müllerian hormone (AMH): Müllerian duct regression
• Leydig cells produce testosterone: Wolffian duct development into rete testis, epidydimus and vas deferens.
• In absence of these hormones: loss of Wolffianduct, Müllerian duct develops female reproductive tract: oviduct and uterus
http://php.med.unsw.edu.au/embryology/images/7/7f/Testis_001.mp4http://php.med.unsw.edu.au/embryology/images/7/7b/Ovary_001.mp4http://php.med.unsw.edu.au/embryology/images/1/12/Uterus_001.mp4
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Development of the external genitalia
EmbryonicgenitaliaarebipotentialXY:Dihydrotestosterone
XY XX
Bipotential tissue XY XX
Cloacalmembrane
Disappears Disappears
GenitalTubercle Glanspenis Clitoris
GenitalFolds Penisshaft Labiaminora
Genitalswellings scrotum Labia majora
Urethralgroove Disappears Vaginalopening
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Development of the external genitalia
urorectalseptumUrorectal septumseparatesrectumfromurogenitalsinus
XY:BladderandurethraProstate
XX:BladderandurethraUterusandvagina
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Development of the external genitaliaDescentofTestes
GubernaculumInguinalcanalProcessus vaginalis
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Development of the external genitaliaCryptorchidism
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Development of secondary sex characteristicsPuberty
ActivationofspermproductionMasculinizationHairgrowth
ActivationofmenstrualcycleFeminizationHairgrowth
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Development of secondary sex characteristicsPuberty
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Threefactorsthatdeterminegenderphenotype:
1.Geneticsex- chromosomalcomposition:XXorXY- determinedatconception
2.Gonadandurogenitaltractdevelopment- Developmentoftestesorovaries- Definedduringembryonicdevelopment
3.Developmentofsecondarysexcharacteristics- Hormonedependent- Definedduringpuberty
Sex Determination
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SexreversalXXmales:TransferofYchromosme intoXchromosomeXYfemales:androgeninsensitivitysyndrome/mutationsinSry/Sox9
HermaphroditismAmbiguousexternalgenitaliaGonads:bothovarianandtesticulartissues:ovotestes
Hypospadias: Failureofgenitalfoldstofuse
Cryptorchidism:Failureoftestestodescent
Tractabnormalities:unicornate uterus,doubleuterus
Hydrocele: peritonealfluidthroughprocessus vaginalisintoscrotum
Disorders of Sex Development
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Lecture overview
DrAnnemiekBeverdam– SchoolofMedicalSciences,UNSWWallaceWurth BuildingRoom234– [email protected]
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
Disorders of sexual development
DrAnnemiekBeverdam– SchoolofMedicalSciences,UNSWWallaceWurth BuildingRoom234– [email protected]
Resources:http://php.med.unsw.edu.au/embryology/
Larsen’s Human EmbryologyThe Developing Human: Clinically Oriented Embryology