Development of the urogenital system

Question 1

What mesoderm region does the urogenital system arise from?

Answer 1

Intermediate mesoderm

Question 2

In kidney development, it is somewhat unique in that they form in 3 distinct steps/structures. They develop in what direction?

Name the 3 structures

Answer 2

Cranio-caudal

Pronephros

Mesonephros

Metanephros

Question 3

The pronephros, develops in the future “cervical” region of the embryo. It is not a functional kidney - basically formed when the intermediate mesoderm starts to thicken and form solid cell clumps. How many of these clumps do you get?

After they have formed, they regress almost immediately. At the end of what week does this occur?

Answer 3

• 7-10
• End of week 4

Question 4

As the pronephros starts to dissappear, the mesonephros starts to form. This is inferior to where the pronephros has informed, and appears a rod-like structure at the abdominal region. Whilst the mesonephros does the capability to act like a proper kidney, but does NOT.

Some cells from this mesonephron will migrate and contribute to what structure?

Like the prenephros, the mesonephros will also quickly???????

Answer 4

Genital ridge.

Regress.

Question 5

What structure is the “definitive kidney”?

Answer 5

The Metaneprhos

Question 6

The metenephros also forms (as the mesenphros starts to regress) from the intermediate mesoderm, but again a bit lower down. What week does it appear? What week does it become functional?

Answer 6

Appears at week 5

Functional by week 11

Question 7

The Metenephros has two main parts - What are they called (again remember they are formed from the intermediate mesodern)

Answer 7

Ureteric bud

metanephric cap (metenephric mesenchyme also a name for this) - the mesdodern forms mesenchyme around the ureteric bud - TOGETHER THESE STRUCTURES WILL FORM THE DEFINITIVE KIDNEY.

The urteric bud and meteneprhic cap are both budded structrues that are from the MESONEPRHIC DUCT.

Question 8

Outline what the cloaca does

Answer 8

• Required for waste removal from the devloping kidney, as well as for the intestinal and reproductive tracts at the early stages.

Question 9

As mentioned elsewhere, the metenephric mesoderm (metenephric cap) and uteritic duct are both the key intermediate mesoderm derived structures that go on to form the definitive kidney.

What broad category of structures do each of these structures go onto form?

Urine production starts very early on in gestation. How many nephrons would you expect to find in the kidney at birth?

Answer 9

Metenephric mesoderm - Excretory units

Uteritic duct - collecting system

1 million nephrons at birth

Question 10

What is the function of the uteric bud?

Answer 10

Allows urine drainage from the developing kidney

Question 11

In order to consider how the bladder and the urethra form - we need to start thinking about the cloaca. The cloaca is hind gut in origin, and has an endodermal lining.

The cloaca must be divided, so that it can form exits for both the uro/genital and digestive systems. What weeks does this happen? What structures form?

Answer 11

Weeks 4-7.

Urogenital sinus anteriorly - which will form the bladder (as well as imput from caudal parts of mesonephric duct)

Rectal/anal canal posteriorly

Question 12

Let’s look at how division of the cloaca leads to formation of the primitive bladder and anal/rectal canal.

Cloacal membrane will be typically found at the end of the embryo. In this membrane, a septum begins to form at the hindgut, which separates out where the rectum and primitve bladder will be. This septum travels in what direction? What is the name for this septum?

What region separates the two

Answer 12

Anteriorly

Uro-rectal septum

Perineal body

Question 13

Whilst division of the cloaca forms the primitive bladder, further work must be done to make the full bladder. The bladder comes from the Cranial part Urogenital sinus. The only part that does not is what, and where does it come from?

What type of lining is the bladder?

Answer 13

• Trigones
• Mesenephric duct

Endoderm

Question 14

At what week do gonads get male or female characteristics?

Answer 14

Week 7

Question 15

The first part of genital duct development is known as the “indifferent stage”. The intermediate mesoderm will form the gonads. Along side the gonads, we get two pairs of genital ducts. These will become fully formed at weeks 5-6. One set of the ducts are associated with the female, whilst the other are associated with the male. Which is which?

Answer 15

Paramesonephric ducts (Mullerian) ducts - more laterall

Mesonephric (Wolffian) ducts

Question 16

The mesonephric duct has a few roles. Firstly, it drains urine from the mesonephric kidney. They also play a really important role in the development of the male reproductive system this is HIGHLY hormone driven.

In males, this fate of this structure is determined by Testosterone. What structures are formed?

Conversley - what happens to the mesenphric duct in the female after the kidney has developed?

Answer 16

• Ductus deferens
• Ejaculatory duct
• Epidiymys

In females, it disappears - does leave a few non-functional remenants though.

Question 17

How do the paramesonephric ducts (lateral to both gonads and mesonephric duct) contribute to genital duct development in females? What happens to them in males?

Answer 17

• The ends of the paramesonephric ducts start to widen - this forms the funnel shaped end of the uterine tubes - open into the peritoneal cavity
• They then undergo a lot of migration caudally, parallel to the mesonephric ducts until they reach the future pelvic region
• Once that happens, they come together and FUSE at the caudal end - thus forming the uterus and the top part of the vagina
  
  • important to note that the more cranial parts do not fuse and form the uterine ducts

MALES

• degenrate - due to the action of anti-mullerian hormone (ALH)

- made by the sertoli cells in the testis.

Question 18

We have looked at the gentical duct development. Let us look at gondal development. This starts primarily at week ????

Gonads initially appear as a little bumps in intermediate mesoderm. (!Note that germ cells are not yet present in these structures). These bumps are known as what?

Answer 18

5

Pair of Urogenital ridges/gonadal ridges

Question 19

An interesting point on gonadal development - the cells that will go onto form egg cells and gametes come from OUTSIDE the gonads. The primordial germ cells come from the epiblast, where they then migrate through the primitive streak and then reside amongst endoderm cells in the yolk sac (basically outside of the main embryo) at around Week?????

Why? Nobody knows. At around Week ????, the primordial germ cells migrate along the ????, arriving at the ?????? at around week ????, and invade the ??????? in the 6th week.

Answer 19

he primordial germ cells come from the epiblast, where they then migrate through the primitive streak and then reside amongst endoderm cells in the yolk sac (basically outside of the main embryo) at around Week 3

At around Week 4, the primordial germ cells migrate along the dorsal mesentery of the hindgut, arriving at the primitive gonads at around week 5, and invade the urogenital/gonadal ridges in the 6th week.

Question 20

Suggest a reason why the germ cells might move out and move back in?

Answer 20

May protect them from all of the signalling that is going on with nervous system formation.

Question 21

If primordial germ cells fail to reach the urogenital ridges, the primitive gonads (or indeed the mature gonads) will not develop - demonstrating the inductive influence that primoridial germ cells have on the gonads.

Question 22

Shortly before and during arrival of primordial germ cells to the primitive gonads, the epithelium of the ????? proliferates, and epithelial cells pentrate the underylying mesenchyme.

When the primordial germ cells reach the urogenital ridges, they form a number of irregularly shaped cords - called ?

Answer 22

Shortly before and during arrival of primordial germ cells to the primitive gonads, the epithelium of the urogenital ridge proliferates, and epithelial cells pentrate the underylying mesenchyme.

When the primordial germ cells reach the urogenital ridges, they form a number of irregularly shaped cords - called Primitive sex cords, on top of the proliferating epithelium.

Question 23

If a Y chromosome is present, what gene acts on the somatic cells to cause further proliferation of the primitive sex cords? If it is not present (i.e. in females), what happens to the primitive sex cords?

Answer 23

SRY - Sex determining region of Y chromosome

Basically the dont get to proliferate and instead start to dissociate.

Question 24

If SRY is present then males are go for launch. The cords (remember now reffered to as Medullary/Testis cords) will undergo the further proliferation, making them look horseshoe shaped. The primitive germ cells move in and mix with somatic cells.

• This movement breaks up with cords into tubules
• The somatic cells start to differentiate into ????? and ???? cells
  
  • First cells produce testosterone - and lots of it
  • second cells produce Anti-mullerian hormone which gets rid of the paramesonphric duct
• You then get a dense connective tissue around the gonad , forming the tunica albuginea - separating the cords from the surface epithelium

Answer 24

Leydig

Sertoli

Question 25

Testis cord remain solid until puberty, where the form a lumen - making them turn in the ????????. Once they are canalised, they join the retis testis, efferent ductules and then the mesonephric duct **(which forms what?)**

Answer 25

Testis cord remain solid until puberty, where the form a lumen - making them turn in the seminiferous tubules. Once they are canalised, they join the retis testis, efferent ductules and then the mesonephric duct **- forming the epididymys and ductus efferents**

Question 26

Female has said to have been the default condition - however this is not the case. There are **active signals required for commitment to female gonad. . What gene is this?**

Answer 26

* Wnt4 - thought of as the ovary determining gene. * WNT4 k/o mice have no paramesoephric ducts.

Question 27

So what are the stages that lead to fermale gonad development? Need to be XX and not have SRY. The primitive sex cords will the dissocitae in clusters - not that they are not **tubular structures like those we saw in men - that are full of primitive germ cells. The clusters are located in the MEDULLARY (i.e centerish parts) part of the ovary.** The surface epithelium contibues to proliferate a lot - this is important as at around week 7 it gives rise to **second generation of cords**- which penetrate the underlying mesenchyme - called ??? cords. The primitivee germ cells that have made it to the gonadal ridge dividing by mitosis - to produce the pool of ????? -which **then enter miotic arrest** (at around 4 months) . Obviously these oocytes need follicular cells to form the primordial follices - this is where the **new cords come in - these cells split into isolated clusters. These clusters continue to proliferate andsurround each oogonium with a layer of epithelium called ?????? cells - thus forming primordial follices.** **NOTE - That follicular cells are just primitive theca and granulosa cells**

Answer 27

Cortical cords Oogonia Follicular cells

Question 28

Brief summary of formation of male and female gonads primitive germ cells migrate to the genital/gonadal ridge and form the **primitive sex cords in _both male and female._** * Males * primitive sex cords develop into medullary/testis cords * Secondary **coritcal cords fail to develop** * Females * primitive sex cords regress - no medullary/testis cords * Secondary **cortical cords develop from the epithelium**

Question 29

Development of the external genitalia starts at around week ???? after fertilisation. It is makred by pair of **cloacal folds developing around the cloacal membrane.** These cloacal folds will fuse together to form a structure called the???, cranial to the cloacal membrane. This structure will go onto form ???? in males and the ???? in females. Caudally, the cloacal folds are **subdivided into the ????? folds anteriorly and the ???? folds posteriorly.** On each side of the urethral folds (**form labia minora in females,whilst cover the male urethra in the penis**) another pair of cellular aggregations called the **genital swellings form. In the male,these will form the ????, and in the female they will form the ????**

Answer 29

Genital tubercle glans Penis Clittoris Urethral folds and anal folds Scrotum and labia majora Obviously when their is either a male or female pathway - all of the decisions will be governed by HORMONES.

Question 30

Let's have a look at the devlopment of the urethra. It forms from **the middle part of the urogenital sinus - whic remember is formed by the divisin of the cloaca.** ## Footnote **In males the process is driven by androgens. The androgens from the fetal testis cause the genital tubercle structure to elongate and become the ????. The \<\<\<\< pulls the urethral folds (previously cloacal folds) forward so they form the lateral walls of the urethral grove and eventually, the urethral folds close over the urethral plate to form penile urethra.** **The terminal part of the male (external urethral meatus) forms from surface ectoderm.**

Answer 30

Phalus

Question 31

Prostate glands develop as outgrowths from what part of the urethra? Bulbourethral glands develop from what part of the urethra?

Answer 31

Prostatic urethra Penile urethra

Question 32

As mentioned before, paramesonephric ducts fuse together to form the top part of the vagina and the uterus. The **lower part of the vagina has different origins- comes from the ????. This produces two outgrowths called sinovaginal bulbs. These bulbs proliferate and form a solid vaginal plate- this will eventually become canalised.**

Answer 32

Urogenital sinus.

Question 33

Variations and things that can go wrong in the development of the female reproductive tract. Double uterus - failure of fusion of the **paramesonephric ducts** **Vaginal atresia - failure of canalisation of the vagina** Absence of vagina and uterus - failure of formation of sinovaginal bulbs. Can also be due to failure of formation of the paramesonpheric ducts - whcih is called Mayar Rokitansky syndrome - the upper vagina and uterus **fail to develop - but lower part of vagina still forms.**

Question 34

What is hypospadias? Incidence?

Answer 34

* Urethra has opening on the underside of the penis * 1in 300 boys - generally very mild - around 70% * Usualy requires surgical correction for urination since opening is on underside rather than on top- makes it difficult to urinate standing up