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DEVELOPMENT OF THE UROGENITAL SYSTEM: M.A.KAI-KAI.

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Presentation on theme: "DEVELOPMENT OF THE UROGENITAL SYSTEM: M.A.KAI-KAI."— Presentation transcript:

1 DEVELOPMENT OF THE UROGENITAL SYSTEM: M.A.KAI-KAI

2 Learning Objectives nephrogenic plategonadal ridgederivatives To understand the nephrogenic plate and the gonadal ridge and their derivatives. originurogenital ridge. To understand the origin, topography and structure of the urogenital ridge. pronephrosinduction mesonephros Understand formation of the pronephros,the induction and formation of the mesonephros and formation of the collecting ducts metanephric diverticulummetanephrogenic mass To know development of the from primordial metanephric structuresl;the metanephric diverticulum and the metanephrogenic mass. nephrogenesis To describe nephrogenesis. genes Brief description of the main genes regulating development of the kidneys. cloacaurogenital sinusderivatives Describe the cloaca, urogenital sinus and derivatives. sex determination Understanding primary and secondary sex determination genetic sex, gonadal sex, phenotypic sex. germ cellsmigration Describe primordial germ cells and the migration to the gonadal ridge. stages Describe stages in gonadogenesis molecular Brief understanding of the molecular aspects of gonadogenesis WolffianMullerian Describe differentiation of the Wolffian and Mullerian ducts into male and female ducts respectively.

3 Overview of development of the urogenital organs Overview of development of the urogenital organs urinary reproductive The urinary and reproductive/genital systems are closely associated in topography,function and development. systems origin intermediate mesodermurogenital ridge The two systems have a common origin from intermediate mesoderm of the urogenital ridge and have homologous structures. internal genital urinary system The internal genital duct system is derived from the fetal urinary system. Malformation of one system affects the other. Intermediate mesoderm interactionsparaxial mesoderm Intermediate mesoderm is stimulated by interactions with adjacent paraxial mesoderm. UGR UGR is longitudinal swelling in dorsolateral side of the abdomen UGR UGR--> formed from: -- non-segmented intermediate mesoderm --proliferation of surrounding mesodermal coelomic epithelium Lateralnephrogenic plate forms urinary organsinternal genital Lateral UGR, the nephrogenic plate forms urinary organs and internal genital ducts. Ventromedialgenital ridge gonads Ventromedial UGR is genital ridge, forms gonads. Paraxial mesoderm Paraxial mesoderm intermediate urogenital interacts with intermediate mesoderm to form urogenital organs. Pax2,Pax8 Paraxial mesoderm message is Pax2,Pax8 (transcription factors).

4 Development of the kidney. Development progresses through three major stages. Two transient stages and third premanent stage. Development progresses through three major stages. Two transient stages and third premanent stage. Three kidneys develop,pronephros, mesonephros and metanephros. Three kidneys develop,pronephros, mesonephros and metanephros. Three kidneys similar in structure and function. Three kidneys similar in structure and function. Pronephros forms. Pronephric tubules degenerate, middle part induce mesonephros,induces metanephros. Pronephros forms. Pronephric tubules degenerate, middle part induce mesonephros,induces metanephros. Similarities of nephric tubules in structure and function in foetal and adult kidneys Similarities of nephric tubules in structure and function in foetal and adult kidneys Efficiency in function. --pronephros --pronephros --mesonephros --mesonephros --metanephros --metanephros

5 Development of the mesonephros(fig.1- 4) Sequence of development. Sequence of development. Mesonephros develops at level of somites 9-26 Mesonephros develops at level of somites 9-26 Pronephros induces formation of mesonephros (MN). Pronephros induces formation of mesonephros (MN). Mesonephric tubules(MT) form from nephrogenic plate as pronephros degenerates. 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). 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). internal glomerulus mesonephric corpuscle BC becomes invaded with a rich vascular internal glomerulus,forming mesonephric corpuscle (MC) Mesonephric tubules darksecretory light collecting Mesonephric tubules differentiate into a thick,dark-staining proximal secretory segment and a thin,light-staining distal collecting segment MT drain into collecting tubule,extend caudally and join existing PD.This mesonephricWolffian mesonephric/Wolffian duct opens in the cloaca cloaca.

6 Development of the metanephros(1) Sequence of development. Metanephros develops at somites from 2 precursors-->metanephric diverticulum (MD)/ureteric bud Metanephros develops at somites from 2 precursors-->metanephric diverticulum (MD)/ureteric bud and metanephrogenic mass (MM) Formation MD and MM is by reciprocal inductive interactions between the tissues. Formation MD and MM is by reciprocal inductive interactions between the tissues. The diverticulum forms caudal of the existing mesonephric duct,grows The diverticulum forms caudal of the existing mesonephric duct,grows craniodorsally into the nephrogenic plate(NP), which aggregates and proliferates into MM. MD urinary duct system MM nephrons The metanephric diverticulum branches as it grows towards the metanephrogenic mass. The metanephric diverticulum branches as it grows towards the metanephrogenic mass.

7 Development of the metanephros(2). The Duct System Development of the metanephros(2). The Duct System Morphogenesis of the metanephric diverticulum. Morphogenesis of the metanephric diverticulum. dichotomous The dichotomous branching pattern is species specific. unipyramidalkidneys renal pelvis Simple,unilobar/unipyramidal kidneys(horse) the proximal end dilates into a renal pelvis papillary/ collecting ducts (CD) collecting tubules (CT) multipyramidal kidneys major calycesminor calyces In multipyramidal kidneys e.g. the MD branches; bifurcates into 2 major calyces and several minor calyces papillary ducts.

8 Development of the metanephros(3). The MM forms the nephrons by nephrogenesis. The MM forms the nephrons by nephrogenesis. MD forms the duct system MD forms the duct systemNephrogenesis Nephrogenesis and differentiation of the metanephric diverticulum are co-ordinated. Nephrogenesis and differentiation of the metanephric diverticulum are co-ordinated. Each collecting tubule grows into a solid cluster of metanephrogenic mass. 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, 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.

9 Development of the metanephros(4) Development of the metanephros(4) Stages in nephrogenesis. Stages in nephrogenesis. Solid cluster of metanephrogenic mass forms and hollows into a renal vesicle(RV) with epithelial lining elongate into metanephric tubules (MT). Solid cluster of metanephrogenic mass forms and hollows into a renal vesicle(RV) with epithelial lining elongate into metanephric tubules (MT). Proliferation,elongation of the MM dependent upon reciprocal tissue interactions using several molecular signals tubules grow centrifugally and form nephrons. Proliferation,elongation of the MM dependent upon reciprocal tissue interactions using several molecular signals tubules grow centrifugally and form nephrons.

10 Development of the metanephros (5). The proximal end of the PCT dilates and invaginates to form the Bowman's capsule The proximal end of the PCT dilates and invaginates to form the Bowman's capsule The DCT attaches to the collecting tubule. The DCT attaches to the collecting tubule. The BC becomes invaded by the glomerulus and the renal corpuscle (RC) is formed. 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. Early RC form in the corticomedullary junction, some degenerate, later nephrons form in the cortex. About 20K(cat) K(dog) nephrons form. About 20K(cat) K(dog) nephrons form. Interstitial connective tissue forms between nephrons, a thick fibrous capsule surrounds the kidney. 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. Nephrogenesis ceases at birth continue for 1-3 wks in the dog and pig. Reciprocal interaction of kidney tissues. 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. 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 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

11 Glial derived neurotrophic factor(GDNF) regulates growth and branching of ureteric bud A.Wild type mouse has normal branching of ureteric bud B. GDNF knock out mouse no branching

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13 Gonadogenesis Gonadogenesis Sex determination-->sequence of interdependent events. Sex determination-->sequence of interdependent events. Primary sex determination at fertilisation genetic sex: XY, XX. Primary sex determination at fertilisation genetic sex: XY, XX. Bipotential gonad Y chromosomes encodes testis-determining factor SRY gonadal sex testis secretes testosterone Bipotential gonad Y chromosomes encodes testis-determining factor SRY gonadal sex testis secretes testosterone Secondary sex determination phenotypic sex. Secondary sex determination phenotypic sex. Absence of Y chromosome forms ovaries Absence of Y chromosome forms ovaries --anti-Mullerian hormone(AMH) regression of paramesonephric duct Wolffian duct forms male genital ducts.

14 Gonadogenesis Gonadogenesis Gonadogenesis occurs at the genital ridge initiated by 2 simultaneous events:- Gonadogenesis occurs at the genital ridge initiated by 2 simultaneous events:- (i).Formation of gonadal cords Degeneration of the mesonephric corpuscles form epithelial cords and invade genital ridge. Degeneration 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. 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 PGC are large,endodermal and migrate from the yolk sac into the developing gonad

15 The indifferent gonad consist of a central core and a peripheral cortex, surrounded by coelomic epithelium. The 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 cat proliferate PGC arrive at the genital ridge at 7,21 days in rodents and cat proliferate epithelial components incorporate PGC, forming gonadal cords. Gonadal differentiation begins. Gonadal differentiation begins.

16 Mechanisms of mammalian primary sex determination Several genes essential for sexual differentiation female is default gonad Several genes essential for sexual differentiation female is default gonad --SRY located on Y-chromosome --sex determination requires interaction between SRY and another factor: SOX9?. Mode of action of SRY 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 --SC secrete glycoprotein;clusterin which initiates testicular differentiation. SOX9 SOX9 --migrates into the nucleus, binds to promoter site of gene for AMH. --activate FGF9? Steroidogenic factor(Sf1) activated by SRY? Steroidogenic factor(Sf1) activated by SRY? --Sf1 could activate Leydig cells and Sertoli cells secreting testosterone and AMH respectively. Wnt4 and Dax1 involved in ovary formation Wnt4 and Dax1 involved in ovary formation --Dax1 suppresses testis formation and activates ovary development.

17 Sex Determination (Modified from Gilbert 2006)

18 Definitive gonads:Testis Y-chromosome produces Y-H which mediates transformation of the sexually indifferent gonad into 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. The Y-H antigen reacts with gonadal cords to form Sertoli cells. Gonadal cords hollow and anastomose into testicular cords enclosing mitotic gonocytes/prespermatogonia Gonadal cords hollow and anastomose into testicular cords enclosing mitotic gonocytes/prespermatogonia Clusterin regulates aggregation of prespermatogonia in the medulla Clusterin regulates aggregation of prespermatogonia in the medulla The cortex develops a thick tunica albuginea, separates the testicular tubules from the germinal epithelium. The 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). Testicular cords (TC) form loops and interconnect with mesonephric tubules(MT). MT differentiate into peripheral seminiferous tubules, central rete testis and efferent ductuli. MT differentiate into peripheral seminiferous tubules, central rete testis and efferent ductuli. WD form epididymis and ductus deferens. WD form epididymis and ductus deferens.

19 Interstitial/Sertoli cells SCs are derived from the epithelial of mesonephric corpuscles and coelomic epithelium.cells proliferate in fetus and postpartum.Mitosis ceases at spermatogenesis. 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. 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 birth Leydig cells(LC) derived from all mesodermal components of the gonadal ridge,proliferate and differentiate,mitosis at birth Testicular cord formation precedes and is essential for differentiation of Leydig cells. Testicular cord formation precedes and is essential for differentiation of Leydig cells. LC cytodifferentiate and secrete testosterone in fetus. LC cytodifferentiate and secrete testosterone in fetus.

20 Definitive Ovary formation. In the absence of the Y chromosome in PGC. Gonadal cords concentrate in the periphery forming the primary ovarian cortex(POC) Gonadal cords concentrate in the periphery forming the primary ovarian cortex(POC) The POC degenerates The POC degenerates and more epithelial cords proliferate and secondary cortex forms. The gonadal cords and germ cells in the medulla degenerate. The gonadal cords and germ cells in the medulla degenerate. The medulla becomes stroma of vascular, lymphatic and nervous tissues The medulla becomes stroma of vascular, lymphatic and nervous tissues Surviving gondal cords form rete ovarii which serves as general morphogenic organiser. Surviving gondal cords form rete ovarii which serves as general morphogenic organiser. Gonocytes continue mitosis fetal life and in early postnatal period. 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 puberty 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 puberty Gonadal cords break up Gonadal cords break up into 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 specific Meiosis in the fetal GC is triggered by meiosis- inducing substances in the ovary which are not species specific Gilbert 2006)

21 Formation of the urogenital sinus[(UGS)fig.8] The cloaca forms the common opening for the urinary and digestive systems. 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 cloaca is bounded caudally by the the cloacal membrane,lying in the proctodeum. The mesonephric ducts enter the cloaca laterally. The mesonephric ducts enter the cloaca laterally. Formation of the UGS begins with division of the cloaca by the mesodermal uroectal septum Formation of the UGS begins with division of the cloaca by the mesodermal uroectal septum The UGS separates the cloaca into dorsal and ventral parts bounded by anal and urogenital membranes. The UGS separates the cloaca into dorsal and ventral parts bounded by anal and urogenital membranes. The membranes degenerate forming the anal and urogenital orifices. The membranes degenerate forming the anal and urogenital orifices.

22 Formation 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 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 and The UGS opens caudally into the amniotic cavity and cranially into the allantoic cavity via the urachus and allantoic 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. 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. The urachus extends into the umbilical cord as the allantoic stalk. Differentiation of the UGS. 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 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. 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.

23 Conginetal Malformations. Renal agenesis lack of development. Renal agenesis lack of development. Dysplasia wide range of abnormal development of nephrons and collecting ducts, form cysts Dysplasia wide range of abnormal development of nephrons and collecting ducts, form cysts Hypoplasia sgenosis of ureter hydronephrosis. Hypoplasia sgenosis of ureter hydronephrosis. Renal hyperparathyroidism. Renal hyperparathyroidism. Ectopic kidneys and ureters. Ectopic kidneys and ureters. Polycystic kidneys failure of nephrons to join collecting ducts? Polycystic kidneys failure of nephrons to join collecting ducts? Rectovaginal constriction hereditary, anovestibular stenosis. Rectovaginal constriction hereditary, anovestibular stenosis. Vesicourachal diverticulum--

24 Summary Summary The urinary system and genital system are derived from the intermediate mesoderm,the nephrogenic plate and genital ridge of the urogenital ridge. The 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 succession pronephros, mesonephros and metanephros in cranial-caudal direction. The kidney develops in three stages in rapid succession pronephros, mesonephros and metanephros in cranial-caudal direction. The pronephros is of limited function in mammals but acts as inducer of the mesonephros. The pronephros is of limited function in mammals but acts as inducer of the mesonephros. The metanephros forms from two precursors the metanephric diverticulum and the metanephrogenic mass.Development of the metanephros requires reciprocal tissue interaction using several molecular signals. The metanephros forms from two precursors the 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. 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. 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. 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 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. The Wolffian and Mullerian ducts form the adult male and female ducts respectively.

25 References 1. 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 ; Noden, M. and de Lahunta(1985). The Embryology of Domestic Animals, pp , Williams and Wilkins, London.


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