Presentation on theme: "DEVELOPMENT OF THE UROGENITAL SYSTEM:"— Presentation transcript:
1DEVELOPMENT OF THE UROGENITAL SYSTEM: M.A.KAI-KAI
2Learning ObjectivesTo understand the nephrogenic plate and the gonadal ridge and their derivatives.To understand the origin, topography and structure of the urogenital ridge.Understand formation of the pronephros,the induction and formation of the mesonephros and formation of the collecting ductsTo know development of the from primordial metanephric structuresl;the metanephric diverticulum and the metanephrogenic mass.To describe nephrogenesis.Brief description of the main genes regulating development of the kidneys.Describe the cloaca, urogenital sinus and derivatives.Understanding primary and secondary sex determinationgenetic sex, gonadal sex, phenotypic sex.Describe primordial germ cells and the migration to the gonadal ridge.Describe stages in gonadogenesisBrief understanding of the molecular aspects of gonadogenesisDescribe differentiation of the Wolffian and Mullerian ducts into male and female ducts respectively.
3Overview of development of the urogenital organs The urinary and reproductive/genital systems are closely associated in topography,function and development.The two systems have a common origin from intermediate mesoderm of the urogenital ridge and have homologous structures.The internal genital duct system is derived from the fetal urinary system.Malformation of one system affects the other.Intermediate mesoderm is stimulated by interactions with adjacent paraxial mesoderm.UGR is longitudinal swelling in dorsolateral side of the abdomenUGR--> formed from:-- non-segmented intermediate mesoderm--proliferation of surrounding mesodermal coelomic epitheliumLateral UGR, the nephrogenic plate forms urinary organs and internal genital ducts.Ventromedial UGR is genital ridge, forms gonads.Paraxial mesoderminteracts with intermediate mesoderm to form urogenital organs.Paraxial mesoderm message is Pax2,Pax8 (transcription factors).
4Development of the kidney. Development progresses through three major stages. Two transient stages and third premanent stage.Three kidneys develop,pronephros, mesonephros and metanephros.Three kidneys similar in structure and function.Pronephros forms. Pronephric tubules degenerate, middle part induce mesonephros,induces metanephros.Similarities of nephric tubules in structure and function in foetal and adult kidneysEfficiency in function.--pronephros--mesonephros--metanephros
5Development of the mesonephros(fig.1- 4) Sequence of development.Mesonephros develops at level of somites 9-26Pronephros induces formation of mesonephros (MN).Mesonephric tubules(MT) form from nephrogenic plate as pronephros degenerates.MT bud off, hollows into the renal vesicle and elongates forming the mesonephric tubule. Proximal end enlarges into a double-walled Bowman's capsule. (BC).BC becomes invaded with a rich vascular internal glomerulus,forming mesonephric corpuscle (MC)Mesonephric tubules differentiate into a thick,dark-staining proximal secretory segment and a thin,light-staining distal collecting segmentMT drain into collecting tubule,extend caudally and join existing PD.Thismesonephric/Wolffian duct opens in thecloaca.
6Development of the metanephros(1) Sequence of development.Metanephros develops at somites from 2 precursors-->metanephric diverticulum (MD)/ureteric budand metanephrogenic mass(MM)Formation MD and MM is by reciprocal inductive interactions between the tissues.The diverticulum forms caudal of the existing mesonephric duct,growscraniodorsally into the nephrogenic plate(NP), which aggregates and proliferates into MM.MDurinary duct systemMMnephronsThe metanephric diverticulum branches as it grows towards the metanephrogenic mass.
7Development of the metanephros(2). The Duct System Morphogenesis of the metanephric diverticulum.The dichotomous branching pattern is species specific.Simple,unilobar/unipyramidal kidneys(horse) the proximal end dilates into a renal pelvispapillary/collecting ducts (CD)collecting tubules (CT)In multipyramidal kidneys e.g. the MD branches; bifurcates into 2 major calyces and several minor calycespapillary ducts.
8Development of the metanephros(3). The MM forms the nephrons by nephrogenesis.MD forms the duct systemNephrogenesisNephrogenesis and differentiation of the metanephric diverticulum are co-ordinated.Each collecting tubule grows into a solid cluster of metanephrogenic mass.The MM has an internal dense medulla which forms the nephrons, and an external,light loose layer which forms the interstitial connective tissue and capsule.
9Development of the metanephros(4) Stages in nephrogenesis.Solid cluster of metanephrogenic mass forms and hollows into a renal vesicle(RV) with epithelial liningelongate into metanephric tubules (MT).Proliferation,elongation of the MM dependent upon reciprocal tissue interactions using several molecular signalstubules grow centrifugally and form nephrons.
10Development of the metanephros (5). The proximal end of the PCT dilates and invaginates to form the Bowman's capsuleThe DCT attaches to the collecting tubule.The BC becomes invaded by the glomerulus and the renal corpuscle (RC) is formed.Early RC form in the corticomedullary junction, some degenerate, later nephrons form in the cortex.About 20K(cat) K(dog) nephrons form.Interstitial connective tissue forms between nephrons, a thick fibrous capsule surrounds the kidney.Nephrogenesis ceases at birth continue for 1-3 wks in the dog and pig.Reciprocal interaction of kidney tissues.The renal precursors; metanephric diverticulum(MD) and metanephrogenic mesenchyme(MM) interact and reciprocally induce each other to form the kidney.Only the MM has the competence to respond to the MD to form kidney tubules and if induced by other tissues, the MM will not respond
11Glial derived neurotrophic factor(GDNF) regulates growth and branching of ureteric budWild type mouse has normalbranching of ureteric budB. GDNF knock out mouseno branching
13GonadogenesisSex determination-->sequence of interdependent events.Primary sex determination at fertilisationgenetic sex: XY, XX.Bipotential gonadY chromosomes encodes testis-determining factorSRYgonadal sextestis secretes testosteroneSecondary sex determinationphenotypic sex.Absence of Y chromosome forms ovaries--anti-Mullerian hormone(AMH)regression of paramesonephric ductWolffian duct forms male genital ducts.
14GonadogenesisGonadogenesis occurs at the genital ridge initiated by 2 simultaneous events:-(i).Formation of gonadal cordsDegeneration of the mesonephric corpuscles form epithelial cords and invade genital ridge.Proliferation of coelomic epithelium invade mesonephric epithelial and resident mesodermal cells.These proliferate forming network of epithelial cords/blastema.PGC are large,endodermal and migrate from the yolk sac into the developing gonad
15The indifferent gonad consist of a central core and a peripheral cortex, surrounded by coelomic epithelium.PGC arrive at the genital ridge at 7,21 days in rodents and catproliferateepithelial components incorporate PGC, forming gonadal cords.Gonadal differentiation begins.
16Mechanisms of mammalian primary sex determination Several genes essential for sexual differentiationfemale is default gonad--SRY located on Y-chromosome--sex determination requires interaction between SRY and another factor: SOX9?.Mode of action of SRY--SRY could activate SOX9(transcription factor)--SRY mediates expression of cell-surface male-specific antigen Y-histocompatibility antigen converting epithelial to Sertoli cells.--SC secrete glycoprotein;clusterin which initiates testicular differentiation.SOX9--migrates into the nucleus, binds to promoter site of gene for AMH.--activate FGF9?Steroidogenic factor(Sf1) activated by SRY?--Sf1 could activate Leydig cells and Sertoli cellssecreting testosterone and AMH respectively.Wnt4 and Dax1 involved in ovary formation--Dax1 suppresses testis formation and activates ovary development.
18Definitive gonads:Testis Y-chromosome produces Y-H which mediates transformation of the sexually indifferent gonad into testis.The Y-H antigen reacts with gonadal cords to form Sertoli cells.Gonadal cords hollow and anastomose into testicular cords enclosing mitotic gonocytes/prespermatogoniaClusterin regulates aggregation of prespermatogonia in the medullaThe cortex develops a thick tunica albuginea, separates the testicular tubules from the germinal epithelium.Testicular cords (TC) form loops and interconnect with mesonephric tubules(MT).MT differentiate into peripheral seminiferous tubules, central rete testis and efferent ductuli.WD form epididymis and ductus deferens.
19Interstitial/Sertoli cells SCs are derived from the epithelial of mesonephric corpuscles and coelomic epithelium.cells proliferate in fetus and postpartum.Mitosis ceases at spermatogenesis.Fetal SC secrete anti-Mullerian hormone(AMH)--> regress paramesonephric ducts.Leydig cells(LC) derived from all mesodermal components of the gonadal ridge,proliferate and differentiate,mitosis at birthTesticular cord formation precedes and is essential for differentiation of Leydig cells.LC cytodifferentiate and secrete testosterone in fetus.
20Definitive Ovary formation. In the absence of the Y chromosome in PGC.Gonadal cords concentrate in the periphery forming the primary ovarian cortex(POC)The POC degeneratesand more epithelial cords proliferate and secondary cortex forms.The gonadal cords and germ cells in the medulla degenerate.The medulla becomes stroma of vascular, lymphatic and nervous tissuesSurviving gondal cords form rete ovarii which serves as general morphogenic organiser.Gonocytes continue mitosis fetal life and in early postnatal period.Some gonocytes begin meiosis and progress to diplotene of prophase I, these become surrounded by single layer of follicular cells then meiosis is arrested till pubertyGonadal cords break upinto primordial follicles containing meiotic and premeiotic germ cells (GC)Meiosis in the fetal GC is triggered by meiosis-inducing substances in the ovary which are not species specificGilbert 2006)
21Formation of the urogenital sinus[(UGS)fig.8] The cloaca forms the common opening for the urinary and digestive systems.The cloaca is bounded caudally by the the cloacal membrane,lying in the proctodeum.The mesonephric ducts enter the cloaca laterally.Formation of the UGS begins with division of the cloaca by the mesodermal uroectal septumThe UGS separates the cloaca into dorsal and ventral parts bounded by anal and urogenital membranes.The membranes degenerate forming the anal and urogenital orifices.
22Formation of the urogenital sinus[(UGS)fig.8] The UGS is divisible into a cranial urethrovesicular and the pelvic UGS and caudal phallic UGS.The UGS opens caudally into the amniotic cavity and cranially into the allantoic cavity via the urachus andallantoic stalk.With growth and expansion of the UGS the mesonephric and metanephric ducts open separately on dorsal wall of UGS at the trigone of bladder.The urachus extends into the umbilical cord as the allantoic stalk.Differentiation of the UGS.In the male,the proximal UVUGS expands into the bladder, the distal part forms the pelvic urethra and the phallic UGS forms the penile urethra.In the female the short urethra forms from the proximal UVUGS, the distal UVUGS and the phallic form the vestibule and part of the vagina.
23Conginetal Malformations. Renal agenesislack of development.Dysplasiawide range of abnormal development of nephrons and collecting ducts, form cystsHypoplasiasgenosis of ureterhydronephrosis.Renal hyperparathyroidism.Ectopic kidneys and ureters.Polycystic kidneysfailure of nephrons to join collecting ducts?Rectovaginal constrictionhereditary, anovestibular stenosis.Vesicourachal diverticulum--<outpockecting of bladder when urachus fails to close.Cryptorchidismfailure of normal descent of testis.Mesonephric or paramesonephric duct abnormalitiesstenotic/aplasia of duct.Pseudohermaphroditegonads of one sex and external gentalia of the opposite sex, hormonal factors.True hermaphroditesgonadal defects at early stage of development, separate gonads or ovo-testis, a chromosomal abnormality.Freemartin cattle intersexuality, a genotypic female(XX) born with normal male co-twin. Fused placental vesselstransport of foetal androgens to female.
24SummaryThe urinary system and genital system are derived from the intermediate mesoderm,the nephrogenic plate and genital ridge of the urogenital ridge.The kidney develops in three stages in rapid successionpronephros, mesonephros and metanephros in cranial-caudal direction.The pronephros is of limited function in mammals but acts as inducer of the mesonephros.The metanephros forms from two precursorsthe metanephric diverticulum and the metanephrogenic mass.Development of the metanephros requires reciprocal tissue interaction using several molecular signals.Sex determination is dependent upon interaction of several factors__. Genetic sex, gonadal sex, hormonal action and phenotypic sex.Germ cells are endodermal, the other tissues are mesodermal. Early in development, germ cells migrate from the yolk sac to the genital ridge.Development of the urogenital system is dependent on molecular signals.The external urinary and genital organs are formed from the cloaca and urogenital sinus.The Wolffian and Mullerian ducts form the adult male and female ducts respectively.
25References1. Gilbert, Scott.F(2003). Developmental Biology. 6th.Edition.pp , , , Sinauer Associate. Massachusetts.2. McGeady, T.A., Quinn, P.J., Fitzpatrick, E.S., & Rayan, M.T., (2006).Veterinary Embryology. Page ;3. Noden, M. and de Lahunta(1985). The Embryology of Domestic Animals, pp , Williams and Wilkins, London.