ORGANOGENESIS OF THE UROGENITAL SYSTEMS.

M.A.KAI-KAI

 the formation of the nephric systems  the formation of the genital ducts  the formation of the gonads  the formation of the external urinary and genital organs .Learning Objectives  This lecture will discuss:  The derivatives of the intermediate mesoderm Incuding.

Overview of organogenesis of the urogenital organs Cr. development.  Malformation of one system affects Mesonephros Gonad (nephrogenic the other. Plate)  The UGR is longitudinal swelling in (genital ridge) dorsolateral side of the abdomen  UGR--> formed mostly from Mesonephric --non-segmented intermediate mesoderm Duct  Lateral UGR(nephrogenic plate) forms Paramesonephric urinary organs and internal genital duct ducts. The Urogenital ridge forms gonads.  Ventromedial UGR is genital ridge. .  Urinary and reproductive systems are closely associated in D V topography.function and Ca. Two systems have common origin from the urogenital ridge(UGR) and have homologous structures. Internal genital duct system is derived from the foetal urinary system.

birds. Vestigial Pronephros (functional in lower fishes) Developing Gastrointestinal tract Progression in time Mesonephric Tubules(higher fishes and Amphibians) Segmented intermediate mesoderm (mesonephros) Mesonephric duct Ureteric bud Unsegmented intermediate mesoderm (mesonephros) Unsegmented intermediate mesoderm Reptiles. The three nephric systems appear in recapitulating sequence during development.The nephrogenic plate differentiates in a rostral to caudal direction and bilaterally.mammals (metanephros) .

Sequence of development of the metanephros(1) Metanephros develops at somites 26-28 from 2 precursors --> ureteric bud(UB) and metanephrogenic mass [A.mesoderm Ureteric bud Collecting ducts Cr D Ca. Metanephros Ureter B .(MM)] Formation UB and MM is by reciprocal inductive interactions between the tissues. The diverticulum forms caudal of the existing mesonephric duct and grows and into the MM at the nephrogenic plate UB forms the duct system MM forms nephrons The ureteric bud branches as it grows towards the metanephrogenic mass(B) Mesonephric duct Urachus Metanephrogenic mass A Bladder Int.

Branching of simple unilobar/ unipyramidal kidneys(dog.horse) the proximal end dilates into a renal pelvis with collecting ducts at the tip In multipyramidal kidneys(ox) ureter bifurcates into 2 major calyces and several minor calyces then collecting ducts cortex medulla renal pelvis ureter collecting duct collecting duct cortex minor calyx ureter medulla major calyx Kidney of ox . Nephrogenesis and differentiation of the ureteric bud are co-ordinated Dichotomous branching pattern of the ureteric bud is species specific.Morphogenesis of the ureteric bud2) The ureteric bud forms the duct Kidney of dog system The metanephrogenic mass forms the nephrons by nephrogenesis.

Development of the metanephros(3) Stages in nephrogenesis. Solid cluster of metanephrogenic mass forms(A) and hollows into a renal vesicle(B) with epithelial lining this elongates into metanephric tubules (C). Collecting duct Fusion Distal Ureteric bud by . Proliferation.elongation of the MM dependent upon reciprocal tissue interactions using several molecular signalstubules grow and form parts of nephrons.

Formation of glomerulus Proximal tube forms PCT.Nephrogenesis. to form of glomerulus Arteriole Bowman’s capsule Collecting tubule Capillary Proximal tubule of nephron Fusion Collecting duct Distal tubule of nephron Arteriole Endothelial layer Fused basal lamina Glomerulus Podocyte layer Structure of renal corpuscle (Bowman’s capsule and glomerulus . BC invaded by the glomerulusforms renal corpuscle (RC). end dilates and invaginates to form the Bowman's capsule(D) Distal tube forms DCT and fuses with the collecting tubule. Nephrogenesis ceases at birth. continues for 1-3 wks in the dog and pig Fusion. Large numbers of nephrons form Interstitial connective tissue forms between nephrons and thick fibrous capsule surrounds the kidney. elongation of nephric tubules and association with capillary.

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

Mesonephric tubule Dorsal aorta Dorsal Genital mesentery ridge Migratiing PGC .And form network of epithelial cords (ii).  Epithelial incorporate PGC. Mesonephric/Wolffian  PGC arrive at the genital duct Glomerulus Arteriole ridge at 21 days cat and proliferate. The bipotential gonad  Gonadogenesis occurs at the genital ridge initiated by 2 simultaneous events:(i).  Gonadal differentiation begins. surrounded by coelomic epithelium. forming gonadal cords.Gonadogenesis(2). migrate from the yolk sac into the bipotential gonad.Formation of gonadal cords  Epithelium from degenerate mesonephric nephrons invade genital ridge.Migration of primordial germ cells.  PGC are endodermal cells.The gonad has a central medulla and a peripheral cortex.

Y chromosomes encodes testisdetermining factorSRYgonadogenesis secretion of foetal hormones by interstitial cells[(Sertoli and Leydig(M).theca cells(F)] secondary sex(phenotypic sex) Anti-Mullerian hormone (Sertoli cells) Regression of Mullerian duct Testosterone (Leydig cells) •Differentiation of Wolffian duct into Male genital ducts •Descent of testis . XX (ii).SEX DETERMINATION Red arrows shows gene regulation Mullerian/ Paramesonephric duct Oestrogen Female genital ducts DAX Wnt 4 Gonadal ridge Bipotential gonad SRY Ovary Testis Primary sex determination at fertilisation (i) genetic sex: XY.

Wolffian duct Rete testis A Definitive gonads:Testis Dorsal mesentery Germ cells and Sertoli cells Testicular concentrate in the testicular cords cords Mullerian duct Fibrous capsule Interstitium The cortex develops a thick Efferent ducts fibrous capsule Testicular cords form loops (seminiferous tubules) and Wolffian duct interconnect with mesonephric tubules to form efferent ducts B Mullerian duct Gilbert 2006 Seminiferous tubules .

Wolffian duct A Dorsal mesentery Ovarian cords concentrate in the cortex The medulla degenerates. In the absence of the Y chromosome in primordial germ cells. lymphatic and nervous tissues. Meiosis begins and is arrested at diplotene of prophase I when epithelia surround germ cells forming primordial follicles. Interstitium Mullerian duct Ovarian cords Germinal epithelium B Wolffian duct Oocyte Primordial follicle Gilbert 2006) . The remnants form the vascular.Ovary formation.

15days dog Mesonephric A duct Metanephrogenic Mesonephros mass Ureteric bud Hindgut Urogenital sinus Anus Cloaca Urachus Urorectal septum Cr V D Ca. .Formation of the urogenital sinus(UGS) The cloaca forms the common opening for the urinary and digestive systems and bounded caudally by the the cloacal membrane. Membranes degenerate forming the anal and urogenital orifice Schematic diagram of lateral view. bounded by anal and urogenital membranes. The mesonephric and metanephric ducts enter the cloaca Formation of the UGS begins with division of the cloaca by the mesodermal urorectal septum separating cloaca into dorsal anus and ventral urogenital parts.

B Uterine horns --The UGS forms penile urethra in male Uterine tube Rectum and vagina in female. Anus  In female(B)Paramesonephric ducts Ovary form female genital ducts. ureter  Mullerian/paramesonephric duct C Epididymis Efferent ducts regresses Ductus deferens Rectum Undescended testis Ureter Bladder Anus Paramesonephric/ Mullerian duct Mesonephric/ Wolffian duct A Prostate gland Descended Testis in scrotum Male Penis .Differentiation of female and male ducts  The UGS opens into the allantoic Hindgut Bipotential cavity via the urachus The UGS is gonad divides into a cranial pelvic region Ureter Cloaca and caudal phallic region. Urachus --The UGS expands into the bladder Urogenital sinus Indifferent Bladder and urethra in both sexes. fuse caudally Vagina Vagina to form uterus and vagina opening & orifice Uterus  In male(C) Wolffian/mesonephric ducts Female Bladder form epididymis and ductus deferens.

 Cryptorchidismfailure of normal descent of testis. form cysts Hypoplasiaagenesis of ureterhydronephrosis. Dysplasiaabnormal development of nephrons and collecting ducts.Congenital Malformations.  True hermaphrodites is chromosomal abnormality during meiosis when the Y chromosome gets a fragment of the X chromosome. RENAL  Renal agenesislack of development.  Pseudohermaphroditegonads of one sex and external gentalia of the opposite sex.  Polycystic kidneysfailure of nephrons to join collecting ducts? REPRODUCTIVE SYSTEM  Rectovaginal constriction at rectovaginal junctionhereditary  Outpockecting of bladder when urachus fails to close. And hormones of both sexes are produced resulting in abnormal external  Freemartin cattle intersexuality. hormonal factors. .  Mesonephric or paramesonephric duct abnormalitiesstenotic/aplasia of duct. a genotypic female(XX) born with normal male co-twin due to fused placental vessels resulting in the transport of foetal androgens to the female. the gonad or ovo-testes gonad formed has both ovarian and testicular tissue.  Ectopic kidneys and ureters.

the nephrogenic plate and genital ridge of the urogenital ridge. germ cells migrate from the yolk sac to the genital ridge. mesonephros and metanephros in cranial-caudal direction. . The external urinary and genital organs are formed from the cloaca and urogenital sinus.Development of the metanephros requires reciprocal tissue interaction using several molecular signals. The metanephros forms from two precursorsthe ureteric bud and the metanephrogenic mass. Three kidneys develops in rapid successionpronephros. Sex determination is dependent upon interaction of several factorsGenetic sex. hormonal action and phenotypic sex. Early in development.Summary The urinary system and genital system are derived from the intermediate mesoderm. Development of the urogenital system is dependent on molecular signals. Pronephros is of limited function in mammals is inducer mesonephros. gonadal sex. The Wolffian and Mullerian ducts form the adult male and female ducts respectively. the other tissues are mesodermal. Germ cells are endodermal.

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