ORGANOGENESIS OF THE UROGENITAL SYSTEMS. M.A.KAI-KAI Learning Objectives This lecture will discuss: The derivatives of the intermediate mesoderm Incuding; 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 Overview of organogenesis of the urogenital organs Cr. Urinary and reproductive systems are closely associated in D V topography,function and Ca. development. 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. 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) Paramesonephric forms urinary organs and internal duct genital ducts. Ventromedial UGR is genital ridge, The Urogenital ridge forms gonads. The nephrogenic plate differentiates in a rostral to caudal direction and bilaterally. The three nephric systems appear in recapitulating sequence during development. Vestigial Pronephros (functional in lower fishes) Developing Gastrointestinal tract Mesonephric Tubules(higher fishes and Amphibians) Segmented intermediate mesoderm (mesonephros) Mesonephric duct Ureteric bud Progression in time Unsegmented intermediate mesoderm (mesonephros) Unsegmented intermediate mesoderm Reptiles,birds,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,(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 Metanephrogenic mass A Urachus Bladder Int.mesoderm Ureteric bud Collecting ducts Cr D Ca. Metanephros Ureter B Morphogenesis of the ureteric bud(2) The ureteric bud forms the duct system The metanephrogenic mass forms the nephrons by nephrogenesis. Nephrogenesis and differentiation of the ureteric bud are co-ordinated Dichotomous branching pattern of the ureteric bud is species specific. 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 Kidney of dog cortex medulla renal pelvis ureter collecting duct collecting duct cortex minor calyx ureter medulla major calyx Kidney of ox 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). Proliferation,elongation of the MM dependent upon reciprocal tissue interactions using several molecular signalstubules grow and form parts of nephrons. Collecting duct Fusion Distal Ureteric bud by Nephrogenesis. Formation of glomerulus Proximal tube forms PCT, end dilates and invaginates to form the Bowman's capsule(D) Distal tube forms DCT and fuses with the collecting tubule. BC invaded by the glomerulusforms renal corpuscle (RC). Large numbers of nephrons form Interstitial connective tissue forms between nephrons and thick fibrous capsule surrounds the kidney. Nephrogenesis ceases at birth, continues for 1-3 wks in the dog and pig Fusion, elongation of nephric tubules and association with capillary, 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 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 Gonadogenesis(1). The bipotential gonad Gonadogenesis occurs at the genital ridge initiated by 2 simultaneous events:(i).Formation of gonadal cords Epithelium from degenerate mesonephric nephrons invade genital ridge.And form network of epithelial cords (ii).Migration of primordial germ cells. PGC are endodermal cells, migrate from the yolk sac into the bipotential gonad.The gonad has a central medulla and a peripheral cortex, surrounded by coelomic epithelium. PGC arrive at the genital ridge at 21 days cat and proliferate. Epithelial incorporate PGC, forming gonadal cords. Gonadal differentiation begins. Mesonephric/Wolffian Dorsal aorta duct Glomerulus Arteriole Mesonephric tubule Dorsal Genital mesentery ridge Migratiing PGC SEX DETERMINATION Mullerian/ Paramesonephric duct Red arrows shows gene regulation DAX Wnt 4 Gonadal ridge Ovary Oestrogen Female genital ducts Bipotential gonad SRY Primary sex determination at fertilisation (i). genetic sex: XY, XX (ii).Y chromosomes encodes testisdetermining factorSRYgonadogenesis secretion of foetal hormones by interstitial cells[(Sertoli and Leydig(M),theca cells(F)] secondary sex(phenotypic sex) Testis Anti-Mullerian hormone (Sertoli cells) Regression of Mullerian duct Testosterone (Leydig cells) •Differentiation of Wolffian duct into Male genital ducts •Descent of testis Wolffian duct Definitive gonads:Testis Rete testis A Dorsal mesentery Germ cells and Sertoli cells Testicular concentrate in the testicular cords Mullerian duct cords Fibrous capsule The cortex develops a thick fibrous Interstitium Efferent ducts capsule Testicular cords form loops (seminiferous tubules) and interconnect with mesonephric tubules to form efferent ducts Wolffian duct B Mullerian duct Gilbert 2006 Seminiferous tubules Ovary formation. In the absence of the Y chromosome in primordial germ cells. Ovarian cords concentrate in the cortex The medulla degenerates. The remnants form the vascular, lymphatic and nervous tissues. Meiosis begins and is arrested at diplotene of prophase I when epithelia surround germ cells forming primordial follicles. Wolffian duct A Dorsal mesentery Interstitium Mullerian duct Ovarian cords Germinal epithelium B Wolffian duct Oocyte Primordial follicle Gilbert 2006) Formation of the urogenital sinus(UGS) Cloaca is common opening for the urinary and digestive systems and bounded caudally by the the cloacal membrane. Formation of the UGS begins with division of the cloaca by the mesodermal urorectal septum separating cloaca into dorsal anus and ventral urogenital parts, bounded by anal and urogenital membranes. Membranes degenerate forming the anal and urogenital orifice Schematic diagram of lateral view.15days dog Mesonephric A duct Metanephrogenic Mesonephros mass Ureteric bud Hindgut Hindgut Urogenital sinus Anus Cr Cloaca Urachus Urorectal septum V D Ca. Differentiation of female and male ducts Mesonephric/ Paramesonephric/ The UGS opens into the A Wolffian duct Mullerian duct allantoic cavity via the urachus Hindgut It divides into a cranial pelvic Bipotential gonad Ureter region and caudal phallic region. Cloaca Urachus --The cranial UGS expands into Urogenital sinus the bladder and urethra in both Indifferent Bladder B Uterine tube sexes. Uterine horns Rectum --The caudal UGS forms penile Anus urethra in male and vagina in Ovary Vagina Vagina female. opening & orifice Uterus In female(B)Paramesonephric ducts form female genital ducts, Female Bladder ureter fuse caudally to form uterus and Efferent ducts C Epididymis vagina Ductus deferens Rectum Undescended In male(C) the Anus testis Wolffian/mesonephric ducts form Prostate gland Ureter epididymis and ductus deferens. Bladder Descended Testis in And Mullerian/paramesonephric Penis scrotum Male duct regresses. Congenital Malformations. RENAL Renal agenesislack of development. Dysplasiaabnormal development of nephrons and collecting ducts, form cysts Hypoplasiaagenesis of ureterhydronephrosis. Ectopic kidneys and ureters. Polycystic kidneysfailure of nephrons to join collecting ducts? REPRODUCTIVE SYSTEM Rectovaginal constriction at rectovaginal junctionhereditary 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 hermaphrodites is chromosomal abnormality during meiosis when the Y chromosome gets a fragment of the X chromosome, the gonad or ovo-testes gonad formed has both ovarian and testicular tissue. And hormones of both sexes are produced resulting in abnormal external genitalia. Freemartin cattle intersexuality, 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. Summary The urinary system and genital system are derived from the intermediate mesoderm,the nephrogenic plate and genital ridge of the urogenital ridge. Three kidneys develops in rapid successionpronephros, mesonephros and metanephros in cranial-caudal direction. Pronephros is of limited function in mammals is inducer mesonephros. The metanephros forms from two precursorsthe ureteric bud and the metanephrogenic mass.Development of the metanephros requires reciprocal tissue interaction using several molecular signals. Sex determination is dependent upon interaction of several factorsGenetic 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. References 1. Gilbert, Scott.F(2003). Developmental Biology. 6th.Edition. pp447-461, 523-540, 548-561, Sinauer Associate. Massachusetts. 2. McGeady, T.A., Quinn, P.J., Fitzpatrick, E.S., & Rayan, M.T., (2006). Veterinary Embryology. Page 233-241; 244-265 3. Noden, M. and de Lahunta(1985). The Embryology of Domestic Animals, pp 312-341, 349-355 Williams and Wilkins, London.