1. ORGANOGENESIS OF THE UROGENITAL SYSTEMS.
M.A.KAI-KAI

2. 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

3. Overview of organogenesis of the urogenital organs
Urinary and reproductive systems are closely associated in topography,function and 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 the other.
The UGR is longitudinal swelling in dorsolateral side of the abdomen
UGR--> formed mostly from
--non-segmented intermediate mesoderm
Lateral UGR(nephrogenic plate) forms urinary organs and internal genital ducts.
Ventromedial UGR is genital ridge, forms gonads.
Cr. V D
Ca.
Gonad
Mesonephros
(nephrogenic
Plate)
(genital ridge)
Mesonephric
Duct
Paramesonephric
duct
The Urogenital ridge

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

5. Sequence of development of the metanephros(1)
Metanephrogenic
mass
Mesonephric duct
Metanephros develops at somites 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) A
Urachus
Bladder
Int.mesoderm
Ureteric bud
Collecting ducts Cr D
Ca.
Metanephros
Ureter B

6. 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
collecting
duct
ureter
collecting duct
cortex
minor calyx
ureter
medulla
major calyx
Kidney of ox

7. 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 signalstubules grow and form parts of nephrons.
Collecting
duct
Fusion
Distal
Ureteric bud by

8. Nephrogenesis. Formation of glomerulus
Fusion, elongation of nephric tubules and
association with capillary, to form 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 glomerulusforms 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
Bowman’s capsule
Arteriole
Collecting tubule
Capillary
Proximal tubule of nephron
Fusion
Distal tubule of nephron
Collecting
duct
Arteriole
Endothelial
layer
Fused basal lamina
Glomerulus
Podocyte layer
Structure of renal corpuscle (Bowman’s capsule and glomerulus

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

10. 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.
Mesonephric/Wolffian
duct
PGC arrive at the genital ridge at 21 days cat and proliferate.
Epithelial incorporate PGC, forming gonadal cords.
Gonadal differentiation begins.
Arteriole
Dorsal aorta
Glomerulus
Dorsal
mesentery
Mesonephric
tubule
Genital
ridge
Migratiing
PGC

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

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

13. In the absence of the Y chromosome in primordial germ cells.
Wolffian duct A
Ovary formation.
Dorsal
mesentery
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.
Interstitium
Mullerian duct
Ovarian cords
Germinal epithelium
Oocyte B
Primordial
follicle
Wolffian duct
Gilbert 2006)

14. Formation of the urogenital sinus(UGS)
Schematic diagram of lateral view.15days dog
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 A
Mesonephric
duct
Metanephrogenic
mass
Mesonephros
Ureteric bud
Hindgut
Hindgut
Hindgut
Urogenital
sinus
Anus Cr
Cloaca
Urorectal
septum V D
Urachus
Ca.

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

16. Congenital Malformations.
RENAL
Renal agenesislack of development.
Dysplasiaabnormal development of nephrons and collecting ducts, form cysts
Hypoplasiaagenesis of ureterhydronephrosis.
Ectopic kidneys and ureters.
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.
Cryptorchidismfailure of normal descent of testis.
Mesonephric or paramesonephric duct abnormalitiesstenotic/aplasia of duct.
Pseudohermaphroditegonads 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.

17. 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 successionpronephros, mesonephros and metanephros in cranial-caudal direction.
Pronephros is of limited function in mammals is inducer mesonephros.
The metanephros forms from two precursorsthe 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 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.

18. 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 ;
3. Noden, M. and de Lahunta(1985). The Embryology of Domestic Animals, pp , Williams and Wilkins, London.