Development of the Urogenital Tract

Question 1

Where does the urogenital system develop from?

Answer 1

The intermediate mesoderm = There is a longitudinal elevation of the intermediate mesoderm on either side of the aorta

This is known as the urogenital ridge = The part of this that forms the urinary system is the nephrogenic cord. And the part that develops into the genital system is the gonadal ridge.

The urinary system develops before the genital`

Question 2

What are the three excretory organs that are present in the embryo at week 3

Answer 2

These secretory organs are arranged cranial to caudal, and as described in this order below:

Pronephros
Mesonephros
Metanephros

All of these form in the 4th week, and are functional at different gestational ages of the foetus

Question 3

Describe the pronephros

Answer 3

Appears at beginning of week 4. THey are non-functional. Are present as 7 solid cell groups in the cervical region.

Everything dissapearas within a week. Only the pronpehric ducts persist and are used by the mesophros next

Question 4

Describe the mesonephros and their relationship with the Wolffian ducts in males and females.

Answer 4

Also appear by 4 weeks. These are functional by the 6-10 week period, and dissapear by week 10. Therefore they are acting as the interim kidneys for 4 weeks.

Origin = From intermediate mesoderm. THey form excretory tubules as well as a tuft of capillaries. These tubules next to the vascular tufts form bowman’s capsules and laterally the tubes open up into the wolffian ducts.

When the mesonephros dissapears = The tubules dissapear but the wolffian ducts persist and participate in the formation of the genitals in the male. But they dissapear in female

Question 5

Describe the metanephros system, its origin,

Answer 5

These form the permenant kidneys and appear in week 5. They start functioning and producing urine in week 12.

Origin = Develop from the metanephric mesoderm.

Collecting ducts = These form instead from the ureteric bud, which is an outgrowth of the mesonephric duct.
Works so that the ureteric bud penetrates the metanephric mesoderm. So that the stalk becomes the ureter, and the expanding part forms the renal calyx.

The mesoderm next to collecting tubule = Forms into metanephric vesicles which later become the renal tubules. They then later get a tuft of capillaries that form the glomeruli.

Question 6

What are the 2 main areas/sources of the kidney.

Answer 6

The metanephric mesoderm = Forms the kidney itself = Renal glomerulus, renal capsule, PCT, loop of henle, DCT.

Ureteric bud = Forms collecting tubule including the renal calyx and the ureter, minor calyx, major calyx, renal pelvis.

Question 7

In renal agenesis, mutations are commonly found in which gene and why

Answer 7

RET PROTEINS/GENE = Have been shown to be important for kidney formation (known as rearranged during transfection protooncogene).

Mutations in this are common in unilateral and bilateral renal agenesis

Question 8

Where is the kidneys location initially and where does it move

Answer 8

Kidney develops in the pelvic region = This is because the metanephric mesoderm is the last one down here on the caudal end.

It ascends later to a more cranial position = Because of the differential growth in lumbar and sacral regions.

As the kidney ascends it rotations 90degrees, and gets its blood supply from the aorta.

Question 9

What gene is implicated in a Wilm’s tumour and what does this gene do

Answer 9

WT1 gene = Regulates the mesoderm to respond to induction by the ureteric bud.

Question 10

Describe when renal agenesis occurs, and what makes it more commn

Answer 10

Occurs when ureteric bud fails to contact and/or induce the metanephric mesoderm.

Renal agenesis more common on left side in males.

Unilateral renal agenesis = Associated with single umbilical artery.

Bilateral renal agenesis = Associated with oligohydramnios and chatacteristic facial appearance

Question 11

When does duplication of the ureter occur? What are the different variations?

Answer 11

Due to early splitting of the ureteric bud.

The split can be partial or complete, and it can have the metanephric tissue also split or not.

Partial division = divided kidney with a bifid ureter.

Complete division = Double kidney with bifid ureter.

Question 12

Why do accessory renal arteries remain?

Answer 12

The arteries are supposed to dissapear as the kidney ascends and gains a new blood supply from aorta. But in 25% of adult kidneys there are 2-4 arteries per kidney.

Question 13

When does the bladder form

Answer 13

From weeks 4 to 7

Question 14

Outline how the baldder is formed

Answer 14

Cloaca = This is divided in half with the urogenital sinus anteriorly and the anal canal posteriorly. These are speerated by the urogenital septum

Urogenital septum = Made of a layer of mesoderm and its tip forms the perineal body.

Urogenital sinus = Then divides into 3 parts

The cranial part = Forms urinary bladder which is continuous with the allantois (formed from yolk sac)

Middle part = Is the narrower part that forms the prostatic and membranous urethra in males, or the entire urethra in females

Caudal or phallic part = Forms the genital organs.

Question 15

What does the allantois later become and how

Answer 15

The allantois becomes the urachus = The medial umbilical ligament.

It does this by having the lumen of the allantois obliterate.

Question 16

How come the trigone is mesodermal in origin, and the rest of the bladder comes from the cloaca?

Answer 16

During development of the bladder = The caudal parts of the mesonephric ducts are absorbed into the bladder.

And the ureters join the bladder as well

Both the mesonephric ducts + ureter are mesodermal in origin = So this area where they join is the trigone. In the trigone there is the incorporation of the ureteric and ejaculatory ducts which are all mesodermal in origin

Question 17

What is the origin and development of the urethra, and how the prostate in men and paraurethral/urethral glands in women come from.

Answer 17

Both male and female = Epithelium of the urethra is endoderm. While the sorrounding connective tissue and SM is mesoderm.

The cranial part of urethra = In males forms the prostatic urethral epithelium with outgrowths to form prostate

In females = Cranial part gives rise to urethral and paraurethral glands

Question 18

How does a urachal fistula form

Answer 18

When the lumen of the intraembryonic portion of the allantois persists.

This means that urine drains to the umbilicus.

If there is only a small persisting area then a small urachal cyst forms.

This is because the allantois connects the bladder to the umbilicus (remember the medial umbilical ligament)

Question 19

Tell me about congenital megacystis

Answer 19

This is a pathologically large bladder = Occurs due to maldevelopment of the ureteric bud

Clinically = Associated with renal failure, pulmonary hypoplasia without intrauterine treatment.

Question 20

What causes exstrophy of the bladder

Answer 20

This is when there is a lack of mesodermal migration AND incomplete closure of the inferior abdo wall between umbilicus and genital tubercle. With a rupture of the thin layer of ectoderm

Clinical = Causes protrusion of the posterior wall of the bladder

Complete exstrophy = Associated with epispadias and seperation of the pubic bones

Question 21

What is exstrophy of the cloaca

Answer 21

Failure of migration of mesoderm to the midline

Clinical = Get exostrophy of the bladder (can see bladder sticking out of anterior lower wall), spinal defects, imperforate anus, and usually omphalocoele.

Question 22

What are the 3 embryological parts of the genital system

Answer 22

Gonads, gonadal ducts, and external genitalia.

Initially they can be male or female, and later on decide

Question 23

Where do the gonads form from and at what time does gonadal development start

Answer 23

Starts at week 4

Remember forms from the medial side of the mesonephros (the second secretory organ).

Question 24

Outline gonadal development stages up to sex differentiation of the gonad

Answer 24

Primordial germ cells migrate from the yolk sac down to join the genital ridges at week 6.

The sex of the gonad is decided first, and later the sexual differentiation of the genital duct and external genitalia depen on the type of gonad.

The SRY (sex determining region on Y) gene is locate on short arm of chromosome Y and determines gonad sex. With SRY gene the testes form, without it female development.

Question 25

What are the two pairs of genital duct?

Answer 25

The mesonephric of Wolffian ducts

And the Mullerian of paramesonephric ducts. These form a ‘U’ shape as they are connected at the bottom.

Question 26

How does the gonad influence the differentiation of the genital ducts and external genitalia

Answer 26

Remember that the sex of the gonad is decided first and then this decides everything else about the other 2

Testes = Produce Mullerian inhibitign substance that stimulates paramesonephric ducts. It produces testosterone whhich stimulates mesopnehric ducts, and dihydrotestosterone, which stimaultes the external genitalia

Ovaries = Makes oestrogens which also stimulates paramesonephric ducts, and causes the external genitalia to form.

Question 27

Outline the process of genital duct formation in the male.

Answer 27

Testes produce testosterone = Cause the mesonephric/Wolfferian ducts to form the epididymis, ductus deferens, and ejactulatory tract.

Seminal vesicles = Form as outbuddings of the tail of epididymis

Paramesonephric ducts = These degenerate in male to form the appendix estes.

Question 28

Outline the process of genital duct formation in the female

Answer 28

Remember the paramesonephric/Mullerian ducts form a ‘U’ with a connection at the bottom that forms the uterovaginal primordium. The tops open up into the abdominal cavity.

The fused paramesonephric ducts = These give rise to the corpus and cervix, and the myometrium

Mesonephric ducts = Most of this dissapears, but small cranial parts of this persist to form the epoophoron. If the caudal part persists then it can develop into a cyst in the uterus or the vagina known as a Gartner’s cyst.

Question 29

Outline the formation of the external genitalia in the initial sex-indifferent stage

Answer 29

Starts at week 3 = The cloaca starts to fold starting to form a genital tubercle at the cranial fold/end, and the anal fold and the caudal fold/end.

On either side of this urethral fold the genital swellings then start to form which become the scrotal swellings in mena nd labia majora in women.

Question 30

Outline the formation of the male external genitalia

Answer 30

Androgens produced by testes = Genital tubercle elongates and becomes the phallus. As it lengthens it pulls the urethral folds. These then have to wrap around the back of the shaft to fuse in the midline. WHen these fuse they form the penile urethra on the inside.

Ectodermal cells join the urethra from the tip and form the external urethral meatus.

The labioscrotal swellings of genital swellings fuse to form the scortum

Question 31

Describe androgen insensitivity syndrome

Answer 31

Genotypically male, but phenotypically female. So that external genitlalia are female but end in a blind pouch. Uterus and tubes are absent or rudimentary.

Cause = Defect in androgen receptor mechanism

Question 32

Outline hypospadias and why it occurs

Answer 32

This is when the urethral folds fail to fuse, which can happen either near the glans high up or at the shaft or en base of penis.

Cause = Inadequate production of androgens by the foetal testes

Question 33

Outline epispadias and why it occurs

Answer 33

Occurs when the genital tubercle is not at the cranial end of the cloacal membrane, but instead is at the urorectal septum.

Outcome = Means the urethra is on the dorsum of the penis. It is often associated with exstrophy of the bladder

Question 34

Outline the formation of the external genitalia in females

Answer 34

Remember the paramesonephric ducts reach down to the urogenital sinus. Two solid evaginations grow from this urogenital sinus = Known as the sinovaginal bulbs. These then proliferate and turn into the solid vaginal plate

Proliferation of the cranial end of the solid vaginal plate = continues until it reaches the cervix.

Later the vaginal plate develops a lumen by central cells breakin down and it forms the vagina.

In the presence of oestrogens = Genital tubercle here also elongates and forms the clitoris.

The urethral folds here = Form the labia minora

Genital swellings = Enlarge and form the labia majora

Urogenital groove = Forms the vestibule

Question 35

Describe the descent of the testes including times

Answer 35

The gubernaculum extends from the testis to the anterior abdo wall. As the foetus grows the testes descend through the inguinal canal.

Testis reaches inguinal canal by week 12, migrates through canal by week 28, reaches scrotum by 33.

Testes gets covered in peritoneal coverings called the processus vaginalis.

Question 36

Outline why absence of the vagina and uterus can occur

Answer 36

Failure of the sinovaginal bulbs to develop and form the solid vaginal plate.

This is usually also associated with an absent uterus

Question 37

Outline why vaginal atresia can occur

Answer 37

This is due to failure of the central cells of the solid vagina plate to die and form the channel. Or failure of the canalisation of the vaginal plate.

Leads to the formation of a transverse vaginal septum usually at the juntion of the middle and superior thirds of the vagina.

Question 38

Outline the definition and cause of cryptorchidism

Answer 38

Undescended testes can occur in 30% of premature infants, and 3-4% of term ones.

IN most cases the testis will descend into scrotum by 1 year. If they remain, then sterility is common

Cause = Deficient production of androgens by the foetal testes can be a role.