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) forms Paramesonephric urinary organs and internal genital duct 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

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,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
Urachus

Metanephrogenic mass

Bladder

Int.mesoderm

Ureteric bud
Collecting ducts

Cr D Ca.
Metanephros

Ureter

Morphogenesis of the ureteric bud2)

The ureteric bud

forms the duct

Kidney of dog

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

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 Bowmans 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 (Bowmans 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(2). 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.
Mesonephric/Wolffian PGC arrive at the genital duct Glomerulus Arteriole ridge at 21 days cat and proliferate. Epithelial incorporate PGC, forming gonadal cords. Gonadal differentiation begins. Mesonephric tubule

Dorsal aorta

Dorsal Genital mesentery ridge

Migratiing PGC

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, 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)

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

Rete testis

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

Ovary formation.
In the absence of the Y chromosome in primordial germ cells.

Wolffian duct

Dorsal mesentery

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.

Interstitium Mullerian duct Ovarian cords

Germinal epithelium

B
Wolffian duct

Oocyte
Primordial follicle Gilbert 2006)

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. 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, 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
Urogenital sinus

Anus Cloaca
Urachus Urorectal septum
Cr

Ca.

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. 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, 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. ureter Mullerian/paramesonephric duct C Epididymis Efferent ducts regresses Ductus deferens Rectum
Undescended testis Ureter Bladder Anus Paramesonephric/ Mullerian duct Mesonephric/ Wolffian duct

Prostate gland
Descended Testis in scrotum

Male

Penis

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 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.