Development if the urogenital system

Question 1

Where does the urogenital system originate from?

Answer 1

intermediate mesoderm

Question 2

What are the structures formed prior to the kidney?

Answer 2

o Pronephros – cervical region
o Mesonephros – abdominal region
o Metanephros – pelvic region

formed in a cranial to caudal and chronological sequence

Question 3

Describe the pronephros

Answer 3

 Rudimentary and non-functional
 Mesoderm solidifies into cell clusters
 7-10 solid cell groups form in the cervical region
 These cell clusters are called the PRONEPHROS
 Cells organise themselves to try and emulate what a kidney should look
like
 Regresses by week 4 – once they form, disappear after clustering
(so never functional as a kidney)
 This is like the “fore-kidney”
 Tubules don’t do much, disappear early
o probably because don’t have time to become functional before disappear

Question 4

What is the mesonephric duct?

Answer 4

– very important structure
o Associated with the mesonephros
o Appears around week 5
o Does not disappear when the rest of the mesenephros does  duct system remains
o Tubules from mesonephros drain into the mesonephric duct at this stage
o NB: Although it is functional as a kidney and forms tubule shapes that have all the necessary
equipment to become functional, it does not go on to form the functional kidney
o Rudimentary in humans but has functions in other animals

Question 5

Describe the metanephros

Answer 5

 appears in week 5 after degeneration of mesonephros
 Fully functional by week 11 (produces urine from week 11/12)
 Forms excretory units of mature kidney
 Excretory units develop from metanephric mesoderm

formed from 2 distinct parts:

• Ureteric bud
• Metanephric cap

Question 6

Describe the uteric bud

Answer 6

 Outgrowth in the bottom of the mesonephric duct
 Derived from intermediate mesoderm
 Source of all duct systems of the kidney
 Becomes associated with the cells in the vicinity – metenephric mesenchyme
 Forms a circular area surrounding the ureteric bud  metanephric

Question 7

Describe the metanephric cap

Answer 7

 Mesenchyme
 Becomes associated with cells in the vicinity of the ureteric bud
 Forms a circular area surrounding the ureteric bud

Question 8

Cloaca:

Answer 8

o Structure at the bottom of the developing gut
o Posterior orifice that serves as the only opening for the
intestinal, reproductive and urinary tracts at early stages
o Acts like a sewer at the bottom end of the embryo
o Collects waste – urine and digestive waste
o Lined with endoderm

Question 9

Ureteric bud:

Answer 9

o Protrusion of mesonephric duct

o Allows urine drainage from the developing kidney

Question 10

Allantois

Answer 10

o Sac like structure involved in nutrition and excretion
o Invagination of hindgut
o Greek for “sausage shape”
o Not functionally developed at this stage in humans
o Vessels in the allantois become important in the vessels of the umbilical cord
o Taken over by the placenta later in development => route to the umbilicus

Question 11

Urachus:

Answer 11

o Duct between the bladder and yolk sac

o Forms from the allantois at around 5-7 weeks

Question 12

Give an overview of the formation of the bladder and urethra

Answer 12

 The cloaca is hindgut to begin with (Endodermal lining)
 Urorectal septum divides cloaca into two halves by fusion with cloaca
membrane to form:
o Anterior urogenital sinus  forms the bladder
o Posterior rectal/anal canal  exit for digestive waste
o Happens between weeks 4-7
 NB: septum is mesodermal in origin
 Bladder forms from the urogenital sinus and caudal parts of the
mesonephric duct

Question 13

Describe the division of the cloaca

Answer 13

o Septum pushes through until it reaches the membrane
o Critical to separate digestive/urinary waste

 Everything above it gives rise to the bladder
 Ureter needs to grow from bladder into the kidney to connect things together => provide a natural exit
for excretory waste

Question 14

Describe the formation of the bladder

Answer 14

 Forms from cranial part of the urogenital sinus
o Apart from the trigone region
 Right at the back of the bladder
 Derived from mesonephric ducts
 All of the mesonephric duct that grows into the bladder becomes absorbed
 Ureter starts to grow out from where the mesonephric duct used to be
 Bladder is lined with endoderm
 Endoderm lining the bladder is derived from the cloaca, but the structures
surrounding it are mesodermal in origin

Question 15

When does the genital system develop?

Answer 15

 Genetic sex is determined at fertilisation
 Gonads do not acquire male or female morphological characteristics until week 7
 Development then follows a sequence of events

Question 16

What are the three sections of reproductive tract development?

Answer 16

Three main sections:

1. Genital duct development
2. Gonadal development
3. External genitalia development

Question 17

Describe the genital duct development during the indifferent stage

Answer 17

 2 pairs of genital ducts develop in weeks 5-6

 Form laterally to the mesonephric ducts (Wolffian) = MALE
o NB: females initially have mesonephric ducts, but they need testosterone to be maintained
o This only happens in males; without testosterone, the
mesonephric ducts degenerate

 The paramesonephric ducts (Mullerian) = FEMALE
o Develop lateral to mesonephric ducts

Question 18

What are the mesonephric (wolffian ducts)?

Answer 18

 Drain urine from the mesonephric kidney

 Switch from being a kidney structure to a reproductive structure

Question 19

What is the function of the mesonephric (wolffian ducts) in the male?

Answer 19

 Play an essential role in the development of the male reproductive system
 Under the influence of testosterone, ducts differentiate to form
o ductus deferens
o ejaculatory duct
o These develop when mesonephros vanishes

Question 20

What is the function of the mesonephric (wolffian ducts) in the female?

Answer 20

o mesonephric ducts almost completely disappear, leave a few non-functional remnants
o Females don’t need ductus deferens/ejaculatory duct  therefore does not need to be
maintained (redundant)

Question 21

How do the paramesonephric (mullerian) ducts develop in the female?

Answer 21

 Develop lateral to the gonads and mesonephric ducts
 Form funnel shaped cranial ends which open into the peritoneal cavity
o Form infundibulum
 Initially 2 duct structures
 Migrate caudally, parallel to the mesonephric ducts until they reach the future pelvic region

5

o Duct systems migrate into the middle
o Approach each other in the midline
 Cranial portion forms the uterine tubes
 Caudal portions fuse to form the uterovaginal primordium
o Uterus and superior vagina

Question 22

How do the paramesonephric (mullerian) ducts develop in the male?

Answer 22

 Paramesonephric ducts degenerate due to the action of
anti-mullerian hormone (AMH).
o Causes regression of the mullerian
(paramesonephric) ducts

 This is a protein made by the Sertoli cells of the testis

Question 23

Describe the development of the gonads

Answer 23

 Gonads initially appear as a pair of longitudinal ridges – week 5
o Indifferent at this stage
o Urogenital or gonadal ridges => give rise to future gonad
 Mesoderm structure – projecting into the coelomic cavity
o Space in the embryo => mesoderm is growing a lot at this point and growing into the space
o This ridge forms the urogenital ridge => this is where the future gonad comes from

Question 24

How do gametes fill the gonads?

Answer 24

 Gonad comes from mesoderm but needs to be filled by the gametes
o Future eggs and sperm (building blocks of germ cells) need to be in the area where the gonads
are forming as they cannot enter the gonads after they have formed
o Germ cells are derived from primordial germ cells
 Primordial germ cells – originate in yolk sac
o Migrate into the body from the yolk sac (an external area)
o Subset of epiblast cells
 Move into the genital ridge via dorsal mesentery
o Forms the primitive gonads
- The germ line is separate from somatic cells.
- Primordial germ cells form in a “cord like” structure, the primitive sex
cords

Question 25

What happens if the primordial germ cells do not migrate?

Answer 25

 If PGCs don’t migrate into the gonadal ridge by week 6, the ridges develop no further (slightly in males) o There will be no development of the ovary/testis o Surrounding tissue does not respond unless the PGCs arrive  Gonad is “indifferent” until week 7

Question 26

What determines male gonad development?

Answer 26

 If the embryo is genetically male (Y chromosome), the Y chromosome encodes testis determining factor  SRY – Sex determining Region of Y chromosome  This is essentially a gene that will cause formation of a testis  Acts on somatic cells and causes proliferation of the sex cords  Primordial germ cells make their way in and moving around to the genital ridge o Nestle into the somatic cells and arrange themselves into cord-like structures

Question 27

Describe gonad differentiation in the male

Answer 27

 Cords become horseshoe shaped o Cords consist of primitive germ cells and somatic cells, as they have to work together to develop a testis  Cords break up to form tubules  resembles structure of adult testis

Question 28

What is the role of the somatic cells of the testes in development?

Answer 28

 Leydig cells begin to produce testosterone o Foetal population of Leydig cells becomes very active around week 8, producing testosterone  Sertoli cells produce anti-Mullerian hormone o Responsible for degeneration of paramesonephric ducts

Question 29

How do the male cords develop?

Answer 29

 Dense connective tissue forms around the cords, separating the cords from the surface epithelium  Leads to the formation of the tunica albuginea => covering of the testis  Testis cords are solid till puberty o No lumen in the cord until puberty o Sperm production does not start until puberty  Acquire a lumen, forming the seminiferous tubules o Join up with the rest of the duct system o Tubes fill with spermatogonia  Join with the rete testis o Common structure that joins with efferent ductules  Rete testis and mesonephric duct eventually link to form the ductus deferens

Question 30

What determines female gonad development?

Answer 30

 not default condition  Active signals are required for female development, and these must be silenced in males o Wnt 4 - “ovary determining gene” o Wnt 4 knockout mice have no Müllerian ducts, similar human mutation

Question 31

Describe the development of the female gonads

Answer 31

 XX chromosome (or really the absence of SRY)  Similar pattern of development to males, but the end structure is different  Primordial germ cells are necessary o With failure to reach the genital ridge the gonad regresses week 6  no formation of ovary o somatic cells grow from the coelomic epithelium  Surface epithelium continues to proliferate to form the surface of ovary o NB: no formation of horsehoe shape  PGCs (oocytes) organise themselves into an outer layer (roundabout where the cortex is going to be) o Divide by mitosis to form a pool of oogonia  egg cells a woman is born with o enter meiotic arrest at beginning of 4th month of gestation, now called “oocytes” o Oocytes become associated with (surrounded by) follicular cells – granulosa and thecal cells  primordial follicles  These are the somatic cells  Blood vessels form within the medulla region – carry hormones into/out of the ovary

Question 32

When does the external genitalia develop?

Answer 32

 Begins before the gonads are properly formed |  Week 3 after fertilisation

Question 33

Describe development of external genitalia

Answer 33

o A pair of cloacal folds develop around cloacal membrane o Join to form a structure called the genital tubercle, at the cranial end. o At the caudal end, the cloacal folds are subdivided into:  Urethral folds in front  form labia minora in female  Anal folds behind  Genital swellings appear on either side of the urethral folds  Male => form scrotal swellings  Female => form labia majora

Question 34

Describe the formation of the urethra

Answer 34

 Forms from middle pelvic part of urogenital sinus  In males, androgens from foetal testis cause genital tubercle to enlarge into phallus o Elongate to form shaft of penis o Phallus pulls urethral folds upwards and forwards o They form lateral walls of urethral groove and close over urethral plate to form penile urethra o Terminal part of male urethra (external urethral meatus) is derived from surface ectoderm

Question 35

Describe the development of the male accessory glands

Answer 35

o Prostate gland develops as outgrowths from the prostatic urethra o Bulbourethral glands develop as outgrowths from penile urethra

Question 36

Describe the development of the lower part of the vagina

Answer 36

o NB: remember that paramesonephric ducts form top of vagina o Two outgrowths form from urogenital sinus - sinovaginal bulbs  Initial septum separates the two – this degenerates  Outgrowths fuse to form a vaginal plate, which hollows to form a cavity  Results in muscular tube-like structure

Question 37

What is a double uterus?

Answer 37

o failure of fusion o bicornuate uterus – only upper body of uterus involved o bicornuate uterus with rudimentary horn

Question 38

What is vaginal atreasia?

Answer 38

o Failed canalisation, i.e. failure to form tube lumen | o Intercourse is impossible

Question 39

How does the absence of vagina and uterus occur?

Answer 39

o Failure of sinovaginal bulbs or paramesonephric ducts to form properly o Formation of bulbs is normally induced by uterus so uterus is usually also absent

Question 40

What is Hypospadias

Answer 40

congenital disorder of the urethra where the urinary opening is not at the usual location on the head of the penis  urethral folds fail to fuse and urethral opening develops in the wrong area  Affects urination and can lead to infection  Fairly easy to correct surgically  very good surgical outcomes

Question 41

What is Klinefelter’s Syndrome

Answer 41

 47XXY or XXXY  Incidence: 1 in 500 males o Y chromosome therefore genetically male  Infertility, gynaecomastia, impaired sexual maturation  May physically appear female at birth  Leydig cells do not produce enough steroids, low sperm production Klinefelters karyotype  Important to karyotype the child at birth before making decisions as to which sex to raise them as

Question 42

Testicular feminising syndrome

Answer 42

 Genetic males, 46XY  Female external phenotype, internal testes  Testes produce testosterone, but a mutation on the X chromosome causes a deficiency in androgen receptors  Testosterone cannot act on target tissues  Uterus and upper vagina are absent because AMH is produced o Individuals are genetically male but externally appear female

Question 43

What is Turner's syndrome?

Answer 43

```  Sex chromosome constitution XO  PGCs degenerate shortly after arrival at the ridge  Results in failure of gonadal development o “streak gonad” o Rudeminetary structure forms o infantile genitalia o mesonephric duct regression  Wide neck, short stature ```

Question 44

Describe Dihydrotestosterone (DHT)

Answer 44

 Small community in the Dominican Republic  High incidence of inhabitants lacked the gene for 5-alpha reductase  5-alpha- reductase deficiency o Enzyme which converts testosterone to dihydrotestosterone o XY children born looking like girls  Blind vaginal pouch  Enlarged clitoris  Internal testes o At puberty everything changes