Development of the Urogenital System

Question 1

Identify the urinary organs.

Answer 1

• Kidney
• Ureter
• Bladder
• Urethra

Question 2

Identify the male reproductive organs.

Answer 2

• Testis
• Epididymis
• Ductus deferens
• Seminal gland
• Prostate
• Bulbourethral gland
• Penis

Question 3

Identify the female reproductive organs.

Answer 3

• Ovary
• Uterine tube
• Uterus
• Vagina
• Vulva

Question 4

Describe how the germ layers, yolk sac and allantois contribute to the formation of the genito-urinary tracts.

Answer 4

♦ Initially, primary streak and two layers (epiblast and hypoblast).

♦ Sometime later, cells of the epiblast migrate through the primitive streak and occupy the region between the epiblast and hypoblast and create a third layer:
– Epiblast will eventually differentiate to ectoderm
– Hypoblast will eventually differentiate to endoderm
– And this middle layer will become the mesoderm

♦ The mesoderm will be subdivided into paraxial mesoderm, intermediate mesoderm and lateral plate mesoderm:
– Paraxial mesoderm will differentiate into somites (sclerotome, myotome, dermatome) and head mesenchyme
– Intermediate mesoderm will develop into the urogenital system and portions of the suprarenal glands
– Lateral plate mesoderm will become the walls of the body cavities, serous membranes (parietal and visceral peritoneum) and circulatory system (with extraembryonic mesoderm)

♦ The intermediate mesoderm grows into the intraembryonic coelom and forms the urogenital ridge on each side.

♦ Urogenital ridge develops into two ridges: the genital (gonadal) ridge medially and the nephrogenic ridge laterally

♦ The nephrogenic ridge gives rise to three successive nephric structures
• Therefore the intermediate mesoderm is also known as the nephrotome

Question 5

Describe the concepts of the cephalo-caudal folding.

Answer 5

♦ During embryonic development three sets of nephric systems develop in craniocaudal succession from the intermediate mesoderm. These are called pronephros (plural, pronephroi), mesonephros, and metanephros (or definitive kidneys)

Question 6

Describe the development of the pronephros.

Answer 6

In the cervical region of the embryo, first of the nephric structures, the pronephroi develops. Pronephroi are connected to pronephric duct via tubules. The pronephroi never fully develop and regress in week 4

Question 7

Describe the development of the mesonephros and paramesonephros.

Answer 7

♦ More caudally (relative to the pronephros), a mesonephric (Wolffian) duct and paramesonephric (Müllerian) duct start to form in the nephrogenic ridge.

♦ Mesonephros start to appear in the thoracic → lumbar regions while the pronephroi regress
• As more mesonephroi develop caudally, the more cranial ones regress

♦ Meanwhile a pair of mesonephric (Wolffian) ducts also succeeds the pronephric ducts

♦ Mesonephroi connect to the mesonephric ducts

♦ Mesonephric ducts grow caudally to open into the postero-lateral wall of the cloaca that will later become the urogenital sinus when divided by the urorectal septum

♦ The mesonephros is the first functioning kidney, with glomeruli, mesonephric tubules, and a mesonephric duct that drains embryonic urine into the cloaca
• After ten weeks, they also cease to function

Question 8

Describe the development of the metanephros.

Answer 8

♦ Formation of the metanephros begins with the formation of the ureteric buds from the distal mesonephric (metanephric) ducts on ~day 28
♦ The ureteric bud grows towards an area of sacral intermediate mesoderm called the metanephric mesenchyme (blastema)
♦ The ureteric bud begins to bifurcate and branch
♦ The ureteric bud and metanephrogenic tissue form the metanephroi, or definitive
kidneys while mesonephroi gradually regress
♦ Metanephric mesenchyme differentiate into the nephrons, the tubule system of the nephron (proximal and distal convoluted tubules, Henle’s loop), and Bowman’s capsule of the renal corpuscle
♦ The ureteric buds differentiate to the ureters, renal pelvis, major calices, minor calices and the collecting ducts of the kidneys
♦ During the tenth week, the metanephroi become functional

Question 9

What can happen if the collecting ducts do not meet the nephric vesicles ?

Answer 9

If the collecting ducts do not meet the nephric vesicles, renal cysts form within the kidney

Question 10

Describe the process of ascent and rotation of the kidneys.

Answer 10

• The metanephric kidney develops in the pelvis. At this stage, the renal hilum of the metanephric kidneys faces anteriorly
• It ascends on the posterior wall of the abdomen and while ascending, rotates 90° so that hilum faces medially
• The mechanism responsible for the cranial relocation of the kidneys is not understood
• Relocating kidney is progressively supplied by a series of arteries from the dorsal aorta (the original renal artery in the sacral region disappears)

Question 11

Identify possible congenital abnormalities of the kidney.

Answer 11

• Renal agenesis (did not develop, because ureteric bud does not meet with metanephric blastema)
• Pelvic kidney: one or both kidneys fail to ascend
• Horseshoe kidney: inferior poles of metanephric blastema fuse with each other, and then grow (usually stuck with inferior mesenteric artery)

Question 12

Explain what the cloaca is, and describe the formation of the urogenital sinus.

Answer 12

• The caudal end of the gut tube is closed by cloacal membrane
• Part of the primitive gut tube just cranial to the cloacal membrane is expanded and called the cloaca.
• A slim diverticulum of the cloaca, called the allantois extends into the yolk stalk
• During the fourth to sixth weeks, a coronal urorectal septum divides the cloaca
  ♦ Anteriorly into the urogenital sinus, which will develop into urinary bladder, urethra and lower urogenital tract
  ♦ Posteriorly into the anorectal canal, which will develop into proximal 2/3 anal canal
• As the tip of the urorectal septum approaches the cloacal membrane, the anal part of the membrane sinks into the anal pit and the cloacal membrane ruptures
  ♦ As a result the urogenital sinus and anorectal canal open to the exterior.
• The urorectal septum becomes the perineal body
• the roof of the urogenital sinus becomes the urethral plate

Question 13

Describe the further development of the mesonephric ducts.

Answer 13

• As the urogenital sinus (urinary bladder) grows, the mesonephric ducts (Wolffian ducts) and ureteric buds (ureters) become incorporated within the posterior wall of the developing bladder (B)
• During this process, openings of the mesonephric ducts are carried inferiorly (B)
• Therefore the ureteric buds “separate” from the mesonephric duct (C)
• The mesonephric ducts move caudally to open into the urethra as the ductus deferens and ejaculatory ducts (only in males) (D)
• The triangular region of the incorporated mesonephric ducts forms the trigone of the bladder (D)

Question 14

Identify congenital abnormalities of the ureter.

Answer 14

♦ Renal agenesis- does not meet with metanephric blastema

♦ Bifid ureter- ureter branches just before meets with metanephric blastema (normally, branch after meeting)

Question 15

Describe the development of the bladder, prostate, and urethra.

Answer 15

♠ The proximal part of the urogenital sinus becomes the urinary bladder while the allantois closes to become the urachus
♠ The pelvic part of the urogenital sinus becomes
• the urethra and lower 2/3 of the vagina (sinovaginal bulb) in females
• the prostatic and membranous urethra and glandular cells of the prostate in males
♠ Stroma and the smooth muscle of the prostate develop from the mesenchyme
♠ Most distal part of the urogenital sinus (definitive urogenital sinus) is drawn along the floor of the extending genital tubercle as the urethral plate and becomes the penile urethra in males

Question 16

Describe the start of the development of the reproductive system (common to both males and females).

Answer 16

• The development of the reproductive system is closely related to the primitive urinary organs in both males and females, as they share similar common tubular structures
• Intermediate mesoderm gives rise to gonadal ridges as well
• By the sixth week, the germ cells migrating from the ectoderm (wall of the yolk
sac) begin to arrive in the genital ridge
• Coelomic epithelium generates somatic support cells, which will
- differentiate into Sertoli cells in the male
- differentiate into follicle cells (or granulosa cells) in the female
• In the meantime, paramesonephric (Müllerian) ducts form just lateral to the mesonephric ducts
• The reproductive ducts arise from the mesonephric ducts (male) and paramesonephric ducts (female)
• Sexual differentiation occurs from week 8 through to week 12
• As the gonads differentiate from the mesoderm, they remain “tethered” by the suspensory ligament cranially and the gubernaculum caudally
• Gubernaculum extends to the labioscrotal folds

Question 17

Describe the development of the male reproductive system.

Answer 17

♠ Primordial germ cells migrate to the genital ridge
♠ In the presence of Y chromosome, somatic support cells express SRY gene
(sex-determining region on Y chromosome) and
♠ Somatic support cells begin to differentiate into Sertoli cells
♠ Primordial germ cells and somatic support cells develop into testes
♠ Mesonephric tubules develop into efferent ducts
♠ Mesonephric ducts (Wolffian ducts) gives rise to
• ductus deferens, ejaculatory duct and seminal vesicles
♠ Paramesonephric ducts (Müllerian ducts) degenerate (but remain as the appendix testis & the prostatic utricle)
♠ The urogenital sinus develops into the
→ urinary bladder, glandular tissue of prostate gland, bulbourethral (Cowper’s) and paraurethral glands and urethra

Question 18

Describe the process of descent of the gonads (testes).

Answer 18

♠ Testes develop in the lumbar region
♠ For optimal function, the testes should be cooler than the body temperature → outside the body
♠ Between the seventh week and birth, Gubernaculum shrinks to draw the testes down from the tenth thoracic level, through the inguinal canal into the scrotum
♠ When the testes are pulled down behind the peritoneum, they drag the parietal peritoneum and a part of the abdominal wall with them
♠ Each testis takes a loop of parietal peritoneum with it during descent that is known as the processus vaginalis that closes and should remain only as the tunica vaginalis around the testes
♠ Ovaries are also pulled down slightly by the gubernaculum, which will become the round ligament of the uterus

Question 19

Identify possible congenital abnormalities in the descend of the testes.

Answer 19

• Cryptorchidism: Failure of complete descent → Infertility, malignancy
• Indirect inguinal hernia or hydrocele: Patency of the processus vaginalis

Question 20

Describe the start of the development of the female reproductive system.

Answer 20

■ In the absence of Y chromosome…
■ Somatic support cells begin to differentiate into follicle (granulosa) cells
■ Primordial germ cells and somatic support cells develop into ovaries
■ Paramesonephric (Müllerian) duct develops
■ Mesonephric ducts (Wolffian ducts) degenerate regress due to lack of testosterone
→ Remnants of mesonephric duct are Gartner’s cysts near vagina and Epoöphoron and paroöphoron near ovary

Question 21

Describe the development of the uterine tubes, uterus and proximal vagina.

Answer 21

• The 2 paramesonephric ducts (Müllerian ducts) meet in the midline, fuse with each other and with the urogenital sinus (sinovaginal bulb)
• During months 3-5, the paramesonephric ducts zip together in a cranial direction to form the proximal vagina, uterus and cervix
• Further cranially, the paramesonephric ducts stay separate as the left and right uterine tubes (oviducts) with fimbriated ends that are open to the coelomic (peritoneal) cavity
• As the paramesonephric ducts lift off the posterior abdominal wall they also lift peritoneum as the broad ligament

Question 22

Describe the indifferent stages of the development of the external genitalia (common to both males and females).

Answer 22

• The external genitalia form from the labioscrotal folds, urogenital folds, and the genital tubercle.
• Ectodermal ridges raised by underlying mesoderm around the cloacal membrane produce the external genitalia in both sexes
• Male and female genitalia are morphologically indistinguishable in indifferent stage (until week 8)
• The floor of the extending genital tubercle is the urethral plate

Question 23

Describe the development of the male external genitalia.

Answer 23

► In males, the genital tubercle elongates to form the shaft and glans of the penis.
► As the genital tubercle elongates, the urogenital (urethral) folds and the urethral
plate grow with it
► When it grows, the urethral plate becomes urethral groove
► The edges of the urogenital folds move towards each other over the urethral groove & fuse in the midline to create the penile urethra (the urethra “zips-up” from proximal to distal)
► The labioscrotal swellings (folds) fuse to form the scrotum.

Question 24

Describe the development of the female external genitalia.

Answer 24

♪ In the absence of dihydrotestosterone, genital tubercle does not elongate
♪ Labioscrotal and urethral folds do not fuse
♪ The genital tubercle becomes the clitoris
♪ Distal end of the urogenital sinus becomes the vestibule of the vagina.
♪ The urethral (urogenital) folds become the labia minora
♪ Labioscrotal swellings become the labia majora

Question 25

Identify congenital abnormalities of the uterus, uterine tubes, and upper vagina.

Answer 25

• The left and right paramesonephric (Müllerian) ducts fuse in the midline as they connect with the urogenital sinus.
• Anomalies of the uterus, uterine tubes, and upper vagina result from the:
  • absence of one duct (unicornuate uterus)
  • complete absence of fusion (double uterus)
  • varying degrees of fusion of the left and right ducts

Question 26

Identify congenital abnormalities of the urethra.

Answer 26

• Glans hypospadias occur if the glans plate does not canalize
• Penile hypospadias occur if the urethral folds do not fuse throughout its full length, (i.e. the urethra opens on the ventral surface of the penis rather than on the glans)

Question 27

Identify examples of congenital abnormalities related to the fact that urogenital system and anorectal canal have a common origin.

Answer 27

Fistulae can occur between urogenital system and anorectal canal:

• Urorectal fistula
• Rectovaginal fistula
• Rectoperineal fistula

Question 28

Identify the derivatives of the following in the male:

Ureteric bud
Mesonephric ducts
Paramesonephric ducts
Urogenital sinu

Answer 28

1) Ureteric bud: ureter
2) Mesonephric ducts: rete testis, efferent ducts, epididymis, ductus deferens, seminal vesicle, trigone of bladder
3) Paramesonephric ducts: appendix testis and prostatic utricle
4) Urogenital sinus: bladder (except trigone), glandular cells of prostate gland, bulbourethral gland, urethra

Question 29

Identify the derivatives of the following in the female:

Ureteric bud
Mesonephric ducts
Paramesonephric ducts
Urogenital sinu

Answer 29

1) Ureteric bud: ureter
2) Mesonephric ducts: trigone of bladder
3) Paramesonephric ducts: oviduct, uterus, cervix, upper 1/3 of vagina
4) Urogenital sinus: bladder (except trigone), urethra, paraurethral gland, greater vestibular gland, lower 2/3 of vagina, vestibule

Question 30

Identify the derivatives of the following in the external genitalia of the male:

Genital tubercle
Urogenital/Urethral Folds
Labioscrotal Swellings

Answer 30

♦ Genital tubercle: Body and glans of penis + Corpora cavernosum and spongiosum
♦ Urogenital/Urethral Folds (fuse): Ventral aspect of penis + penile raphe
♦ Labioscrotal Swellings (fuse): Scrotum + Scrotal raphe

Question 31

Identify the derivatives of the following in the external genitalia of the female:

Genital tubercle
Urogenital/Urethral Folds
Labioscrotal Swellings

Answer 31

♦ Genital tubercle: Body and glans of clitoris
♦ Urogenital/Urethral Folds (do not fuse): Labia minora
♦ Labioscrotal Swellings (do not fuse): Labia majora + Mons pubis