Development if the urogenital system Flashcards
Where does the urogenital system originate from?
intermediate mesoderm
What are the structures formed prior to the kidney?
o Pronephros – cervical region
o Mesonephros – abdominal region
o Metanephros – pelvic region
formed in a cranial to caudal and chronological sequence
Describe the pronephros
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
What is the mesonephric duct?
– 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
Describe the metanephros
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
Describe the uteric bud
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
Describe the metanephric cap
Mesenchyme
Becomes associated with cells in the vicinity of the ureteric bud
Forms a circular area surrounding the ureteric bud
Cloaca:
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
Ureteric bud:
o Protrusion of mesonephric duct
o Allows urine drainage from the developing kidney
Allantois
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
Urachus:
o Duct between the bladder and yolk sac
o Forms from the allantois at around 5-7 weeks
Give an overview of the formation of the bladder and urethra
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
Describe the division of the cloaca
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
Describe the formation of the bladder
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
When does the genital system develop?
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
What are the three sections of reproductive tract development?
Three main sections:
- Genital duct development
- Gonadal development
- External genitalia development
Describe the genital duct development during the indifferent stage
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
What are the mesonephric (wolffian ducts)?
Drain urine from the mesonephric kidney
Switch from being a kidney structure to a reproductive structure
What is the function of the mesonephric (wolffian ducts) in the male?
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
What is the function of the mesonephric (wolffian ducts) in the female?
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)
How do the paramesonephric (mullerian) ducts develop in the female?
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
How do the paramesonephric (mullerian) ducts develop in the male?
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
Describe the development of the gonads
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
How do gametes fill the gonads?
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
What happens if the primordial germ cells do not migrate?
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
What determines male gonad development?
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
Describe gonad differentiation in the male
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
What is the role of the somatic cells of the testes in development?
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
How do the male cords develop?
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
What determines female gonad development?
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
Describe the development of the female gonads
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
When does the external genitalia develop?
Begins before the gonads are properly formed
Week 3 after fertilisation
Describe development of external genitalia
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
Describe the formation of the urethra
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
Describe the development of the male accessory glands
o Prostate gland develops as outgrowths from the prostatic urethra
o Bulbourethral glands develop as outgrowths from penile urethra
Describe the development of the lower part of the vagina
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
What is a double uterus?
o failure of fusion
o bicornuate uterus – only upper body of uterus involved
o bicornuate uterus with rudimentary horn
What is vaginal atreasia?
o Failed canalisation, i.e. failure to form tube lumen
o Intercourse is impossible
How does the absence of vagina and uterus occur?
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
What is Hypospadias
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
What is Klinefelter’s Syndrome
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
Testicular feminising syndrome
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
What is Turner’s syndrome?
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
Describe Dihydrotestosterone (DHT)
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
