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Development of the Reproductive System Dr Annemiek Beverdam – School of Medical Sciences, UNSW Wallace Wurth Building Room 234 – [email protected] Resources: http://php.med.unsw.edu.au/embryology/ Larsen’s Human Embryology The Developing Human: Clinically Oriented Embryology

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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

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

Threefactorsthatdeterminegenderphenotype:

1.Geneticsex- chromosomalcomposition:XXorXY- determinedatconception

2.Gonadandurogenitaltractdevelopment- Developmentoftestesorovaries- Definedduringembryonicdevelopment

3.Developmentofsecondarysexcharacteristics- Hormonedependent- Definedduringpuberty

Sex Determination

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

Embryonic tissues contributing to development of the reproductive system

IntermediateMesodermCoelomic EpitheliumPrimordialGermCells

Week4embryo

EarlyMesodermDevelopment

1 23 4

NeuralTube

1:notochord2:paraxialmesoderm3:intermediatemesoderm4:lateralplatemesoderm

IntermediateMesodermSegmentedandunsegmentedintermediatemesoderm

MesonephricductUrogenitalsinus

MesonephrictubulesUretericbuds

IntermediateMesoderm3nephricsystems:- Pronephros:regress- Mesonephros:reproductivesystem,andcollectingductandtubulesofthekidney- Metanephros:nephronsofthekidney

Coelomic epithelium

Lateralplatemesodermdevelopsinto:- Splanchnic/visceralmesoderm- Somatic/parietalmesoderm

Intraembryoniccoelom:3cavities:- Pericard- Pleural- Peritoneum

Coelomic epithelium

Gonad developmentPrimordial Germ Cells

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

PGCsariseduringgastrulationPGCsareinitiallysetapartinhindgut/yolksac/allantoisLaterthePGCsmigrateintothegenitalridgesthroughthehindgutintothegenitalridges

Gonad developmentPrimordial Germ Cells

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

PGCsariseduringgastrulationPGCsareinitiallysetapartinhindgut/yolksac/allantoisLaterthePGCsmigrateintothegenitalridgesthroughthehindgutintothegenitalridges

Intermediatemesodermgivesrisetourogenitalsystem:

Gonad development

Ductalsystemdevelopswithinintermediatemesoderm

Threeregionswithinintermediatemesoderm:1.Pronephros:transient2.Mesonephros:

- formsmesonephric (Wolffian)duct- functionalembryonickidney- formsgonads

3.Metanephros:- ductformsuretericbud- formsadultkidney

Mesonephros iscoveredbycoelomic epithelium

Gonad development

�(From:Mousedevelopment,Ch.SexDeterminationanddifferentiation,SwainandLovell-Badge)

Gonad DevelopmentBipotential organs

GenitalRidgesSomaticgonadcellsGermcellsWolffian/MesonephricDuctMullerian duct/Paramesonephricduct

Male:

Testes

EpididymusVasdeferensSeminalvesicle

Ejaculatoryductandinputs:

PenisUrethra

Gonad

Ductalsystemsinmesonephros:Wolffian ductMullerian duct

Genitaltubercle

Female:

Ovary

InfundibulumOviductAmpullaUterusCervix

UpperVagina

LowerVaginaClitoris

Gonad DevelopmentBipotential tissues

Gonad DevelopmentBipotential gonadal cells

Somaticgonadcells:- Supportingcells

- Steroid-producingcellsSertoli cellsLeydig cells

Granulosa cellsThecacells

PrimordialgermcellsSpermatogonia Oogonia

��

(Adapted from Ross and Capel, 2005)

Gonad Development

SomaticgonadcellsinXYgonad:Sertoli cellsfirst,thenfetalLeydig cellsFetalLeydig cellsafterbirthreplacedbyadultLeydig cells

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

Gonad Development

Leydigcells

Sertoli cells

GermcellsMesonephros

Embryonictestis Embryonicovary

��

(Adapted from Ross and Capel, 2005)

?

Gonad DevelopmentSex determination

SomaticgonadcellsinXYgonad:Sertoli cellsfirst,thenfetalLeydig cellsFetalLeydig cellsafterbirthreplacedbyadultLeydig cells

Sry, the male sex determining gene

Ychromosome

Sry is transiently expressed in Sertoli Cells and induces SOX9 expression

Sry expressioninXYgenitalridges

Sry, the male sex determining gene

Female:

Ovary

Mullerian Duct:Infundibulum

OviductAmpullaUterusCervix

UpperVagina

Male:

Testes

Wollfian Duct:EpididymusVasdeferensSeminalvesicleEjaculatoryduct

Urethra

Development of Reproductive Tract

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

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

Development of the external genitalia

urorectalseptumUrorectal septumseparatesrectumfromurogenitalsinus

XY:BladderandurethraProstate

XX:BladderandurethraUterusandvagina

Development of the external genitaliaDescentofTestes

GubernaculumInguinalcanalProcessus vaginalis

Development of the external genitaliaCryptorchidism

Development of secondary sex characteristicsPuberty

ActivationofspermproductionMasculinizationHairgrowth

ActivationofmenstrualcycleFeminizationHairgrowth

Development of secondary sex characteristicsPuberty

Threefactorsthatdeterminegenderphenotype:

1.Geneticsex- chromosomalcomposition:XXorXY- determinedatconception

2.Gonadandurogenitaltractdevelopment- Developmentoftestesorovaries- Definedduringembryonicdevelopment

3.Developmentofsecondarysexcharacteristics- Hormonedependent- Definedduringpuberty

Sex Determination

SexreversalXXmales:TransferofYchromosme intoXchromosomeXYfemales:androgeninsensitivitysyndrome/mutationsinSry/Sox9

HermaphroditismAmbiguousexternalgenitaliaGonads:bothovarianandtesticulartissues:ovotestes

Hypospadias: Failureofgenitalfoldstofuse

Cryptorchidism:Failureoftestestodescent

Tractabnormalities:unicornate uterus,doubleuterus

Hydrocele: peritonealfluidthroughprocessus vaginalisintoscrotum

Disorders of Sex Development

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