Development of the Genital System Flashcards
What is the urogenital system composed of?
Intermediate mesoderm
Coelomic epithelium
Allantois/yolk sac endoderm
what does the intermediate mesoderm give rise to?
Nephrogenic cord –> kidney
Urogenital ridge mesenchyme (located right by the nephrogenic cord)
wha is the coelomic epithelium?
what kind of dermal structure is this?
what does it give rise to?
it is the cells lining the urogenital ridge (hence why its called somatic support cells)
somatic layer of the lateral plate mesoderm
primary sex cords (gonadal) –> gives rise to the testes and ovary
Allantois/yolk sac:
what kind of dermal structure is this?
what resides here and where do those come from?
endoderm
region where the germ cells reside.
the germ cells are coming from the epiblast
mesonephric duct does what?
what is it also called?
gives rise to male internal genitalia.
wolffian duct
paramesanephric
gives rise to female internal genitalia
Mullerian
primordial germ cells:
1) where are they coming from?
2) what are the support cells for each gender that help nurture an environment?
3) where are these support cells coming from?
4) what cells for each gender are producing steroids or the precursors to those steroids?
5) where are these coming from?
coming from the epiblast
they need support from other cells
Male = Sertoli cells –> Coelomic epithelium
Female = Follicle cells –> coelomic epithelium
Male = Interstitial (leydig) cells –> Intermediate Mesoderm
Female = Thecal Cells –> Intermediate Mesoderm
Gametogenesis?
formation of egg and sperm
arise from the epiblast during 2nd week
migrate through the primitive streak (week 3), then reside out in the allantois and yolk sac.
at week 5, they determine it’s safe and they migrate via dorsal mesentery
by week 6 they colonize the urogenital ridge
why are we putting our germ cells out in the yolk sac in week 3?
in week 4, everything is happening so they’re not encountering molecular signals so they’re not inducing the formation of stuff if we tuck them away in the yolk sac
in week 5, they determine it is safe and they leave that area.
Oogenesis?
how many at each stage?
start to form our ovaries in our females.. the number of oogonia go through mitosis to increase
by the 5th prenatal month (in utero), there are 6 million egg cells that have been produced.
by birth, we are down to 1 million and they go through atresia.
the egg cells continue to go through this and by puberty they have about 40,000 eggs left.
in total, only about 400 eggs will be released
Ovulation, what type of duplication is happening?
what about when fertilized?
Meiosis 1 occurs
once the egg is fertilized, then meiosis 2 is occurring
why is it that women that are 35-40 have a higher chance of having a baby with developmental problems?
400-450 will be ovulated throughout their whole lifetime, but they are in a constant state of suspension.. so that’s why they say you have a better likelihood of avoiding chromosomal abnormalities if you’re a younger mother.
35-40, then you can get more chromosomal abnormalities because the eggs have been sitting around for 40 years.
How does sex determination happen?
what are secondary events?
the central event is going to be differentiation of the testes.. which is a genetic event
XY = male, XX = female.
Secondary events are the production of humoral factors by gonads.. which give you your phenotype
testosterone.
so XY and produce testosterone, you phenotypically will look like a man.
XX and do not have testosterone, so you will have a phenotype of a female.
what specifically is on the Y chromosome?
what does it code for?
How do we know what this does and what happens for both male and female?
Sex Determining Region Y Human Gene (SRY)
this gene turns on different genetic pathways. it codes for DNA binding proteins called testis-determining factor (TDF).. this will bind to the DNA and turn on stuff
we’ve done mouse studies..
if we take a genotype male (XY) mouse, and we delete the SRY gene… this mouse is female. looks female, acts female, but is STERILE
if we take a transgenic mouse of XX and we splice in the SRY portion, those mice look male, normal leydig cells, Sertoli cells, sexual behavior, no hermaphroditism.. they are STERILE
so if SRY is present, what kind of genotype do we have?
what does the intermediate mesoderm do then because we have this presence?
XY
this causes the intermediate mesoderm to give rise to the Leydig cells..
these leydig cells produce testosterone, and this testosterone causes the mesonephric ducts to persist!
those remodel and you get INTERNAL MALE GENITALIA
because we have testosterone… we have DHT (dihydrotestosterone), and under that influence we have male EXTERNAL genitalia.
if the SRY gene is present, what does the coelomic epithelium do?
forms Sertoli cells
Sertoli cells produce AMH (anti-mullerian hormone)
AMH is going to cause paramesonephric ducts to degenerate (which would have given rise to internal female genitalia)
What happens if SRY is absent?
what genotype is it?
what does the intermediate mesoderm do because of this?
XX
IM forms Thecal cells
thecae cells do NOT produce testosterone, so if no testosterone, the mesonephric ducts are going to degenerate.. so no male genitalia..
no DHT, so we get female external genitalia.
What happens if SRY is absent to the coelomic epithelium.
CE will form follicular cells
they do NOT produce AMH, which causes paramesonephric ducts to stay, creating INTERNAL female genitalia
Ovotesticular DSD (true Gonadal Intersex)?
the gonads themselves (testes or ovaries) have components of both.
the cause of how this happens is not understood well.
these individuals have both testicular and ovarian tissue and “ovotestis” which is the same meaning
the phenotype may be male or female, but the external genitalia may be ambiguous
46, XX DSD, what happens?
what happens physically? (4 )
what is it caused by usually?
genotypical a female, but the female has been exposed to excessive androgens during development..
your ovaries are present, but external genitalia is masculinized
you get clitoral hypertrophy so it looks like a small penis
partial fusion of labia majora to look like a scrotum
persistent urogenital sinus.
most commonly from Congenital Adrenal Hyperplasia (CAH)
** deficiency in 21-hydroxylase, so excess androgens.. so you’re going to get EXTERNAL male genitalia, and varying parts of how masculinize the genitalia look.
46 XY DSD?
what causes it? (2)
caused by:
inadequate production of testosterone and/or AMH
Androgen insensitivity
we see testicular development is anywhere from rudimentary to normal.. we also may see persistent paramesonephric ducts
external genitalia are female or ambiguous
what is Androgen insensitivity syndrome?
subtype of?
what does it cause?
(subtype of 46 XY DSD)
genotypical you’re a male, but your cells aren’t responsive to the different androgens present.
Testes are present but they have normal external female genitalia
*blind end vagina!
absent or rudimentary uterus / uterine tubes
at puberty, normal breast development and female characteristics, but no menstruation
What will happen if there’s not enough AMH or no AMH? (from an XY since SRY is present)
since Sertoli cells can’t produce that, your paramesonephric ducts are not going to degenerate. (if just a little bit produced, you’ll have some female genitalia)
your leydig cells are going to still produce testosterone, so mesonephric ducts are going to persist
so you’re going to have both internal male and female genitalia (uterus, uterine tubes, vagina), but also external male genitalia
What will happen if you have a 5a-reductase deficiency?
this will not convert testosterone to DHT
so you’re going to not male male external genitalia
you’ll still have mesonephric ducts and the degeneration of paramesonephric… but you will have ambiguous external genitalia (or female external genitalia).
internal male there, external not there. no internal female
Explain gonad development: whole process:
1) where is it happening
2) what week does it start and what happens
3) at what week does it look the same?
gonad development happens in the lumbar region of the embryo.
at week 5 it looks the same on both sexes.
on week 5, we get the formation of the gonadal ride (urogenital ridge) on the medial side of the mesonephros (which was the 2nd kidney)
a wave of cells comes in to form our primary sex cords, these are coming form the coelomic epithelium. they migrate into the developing Gonad.
they persist in males, and degenerate in females.
by week 6, the primordial germ cells have invaded the gonadal ridge
we get a second wave of sex cords coming from coelomic epithelium, and these go AROUND the germ cells and give you the appropriate support cells.
what happens at week 6 during gonad development?
the primordial germ cells have invaded the gonadal ridge
we get a second wave of sex cords coming from coelomic epithelium, and these go AROUND the germ cells and give you the appropriate support cells.
Male gonad development: Testes.
**Primary sex cords come in from the coelomic epithelium and persist
they give rise to the seminiferous cords and Sertoli cells that produce AMH
**connective tissue come from IM and becomes Leydig cells and the Tunica albuginea
Female Gonad Development: Ovary
Secondary sex cords (from coelomic epithelium) are going to stay –> give rise to primordial follicles and granulose cells
Thecal cells come from IM
Germ cells are undergoing mitosis to produce primordial follicles
At the indifferent stage, what happens?
what week is it?
week 5 or 6
we get 2 ducts:
1) mesonephric (part of your second kidney–> male.. degenerates in females
2) paramesonephric duct –> female
both ducts are running the length of the embryo
if we are male, what’s the differentiation of the male duct system?
Sertoli cells are producing AMH which causes the paramesonephric ducts to degenerate
Leydig cells from IM form testosterone, which causes the mesonephric duct to stay and remodel.. which gives rise to the epididymis, ductus deferens, seminal vesicle, ejaculatory duct.
Mesonephric tubules (part of 2nd kidney) –> gives rise to Efferent ducts and Rete Testis
What is a prostatic utricle?
appendix on the testes?
remnant of the paramesanephric duct.
sometimes you can see an appendix on the testicle, which is also a remnant of the paramesanephric duct
what if there’s an appendix on the epididymis?
little bit of tissue left over from the mesanephric duct`
Female, what is the differentiation of the duct system?
cranial and caudal region?
development of the paramesonephric ducts, forming in the lateral coelomic bay
the cranial part gives rise to the uterine tubes
the caudal gives rise to uterovaginal primordial (uterus and vagina)
what happens because we have two paramesonephric ducts in females?
they come caudally and fuse in the caudal region, giving you the uterovaginal primordium
What do the paramesonephric ducts project to caudally? what do they produce?
urogenital sinus –> which is the bladder!
the ducts are going to project to the urogenital sinus and produce the sinus tubercle.
Females in the indifferent stage?
the females do not have testosterone present so the mesonephric ducts are going to degenerate.
parts may persist and we may get the epoophoron and paroophoron which are remnants of the mesonephric duct that you’ll see right next to the ovary (epoophoron) or next to the uterus (paroophoron).
Paramesonephric ducts are going to say because no AMH is being made.
Gartner cysts?
on the lateral wall of the vagina and they are remnant of the mesonephric ducts.
Explain the differentiation of the Uterus and the vagina
starts as a Uterovaginal primordium (fused paramesonephric ducts) –> these contact the urogenital sinus (gave rise to the bladder) –> forms the sinus tubercle.
this tubercle gives rise to sinovaginal bulbs.
those bulbs are endodermal outgrowths that extend and grow and eventually they fuse to form the vaginal plate.
the plate is going to be a tube full of cells. then it undergoes recanalization and you’ll get the hollowed out vagina.
Vagina comes from what two sources?
superior 1/3 comes from paramesonephric ducts (IM)
lower 2/3 comes from hindgut endoderm.
what is the hymen?
small membrane that is coming from endoderm.
it’s kind of a perforated membrane.
Uterus/vagina abnormalities, what fails to happen? (5)
1) paramesonephric ducts didn’t fuse –> 2 vaginas and 2 uterus
2) they fused, but did not fuse completely (mild is an indentation, more severe would be 2 uteruses) –> still have 1 vagina)
3) one of the paramesonephric ducts atrophies
4) the paramesonephric duct atrophies at the most caudal region of the uterus (cervical atresia)
5) vaginal atresia –> no sinovaginal bulbs form, no vaginal plate formed. so no vaginal opening.
What happens to the male urogenital sinus? what are they coming from
1) bladder, urethra
2) prostate
3) bulbourethral glands
4) smooth muscle of prostate
5) ureters
6) epididymis, vas deferens, seminal vesicle, ejaculatory duct
remember that forms the bladder
our bladder was hindgut endoderm, the urethra is also hindgut endoderm
the prostate is forming from the pelvic part of the urogenital sinus (so endoderm)
the smooth muscle of the prostate comes from splanchnic layer of lateral plate mesoderm
bulbourethral glands –> comes from phallic portion of urogenital sinus (so also hindgut endoderm)
ureters coming from intermediate mesoderm
epididymis, vas deferens, seminal vesicle, ejaculatory duct = all come from mesonephric ducts or intermediate mesoderm
Male external genitalia?
what are the players for this?
what does each become?
(under influence of DHT)
on the rostral part of the cloacal membrane we have the genital tubercle.
on that urogenital membrane on either side you’re going to get the urethral or urogenital folds on either side and labioscrotal swellings most laterally..
our genital tubercle in men in the presence of testosterone becomes Glans Penis!
Urethral (urogenital) folds are going to form the lateral walls of the urethra and spongy urethra
labioscrotal swellings are going to become the scrotum
female external genitalia?
what are the players?
what does each become?
on the rostral part of the cloacal membrane we have the genital tubercle.
on that urogenital membrane on either side you’re going to get the urethral or urogenital folds on either side and labioscrotal swellings most laterally..
genital tubercle –> Glans Clitoris
Urethral (urogenital) folds –> stay and form frenulum of labia minora
labioscrotal swellings give Labium majus and Mons Pubis
the spongy urethra doesn’t make it all the way to the external surface, how does it get there?
what’s going to happen as this thing continues to develop?
we have the formation of the navicular fossa. it’s Surface ectoderm that INVAGINATES AND PROLIFERATES!
it meets up with the endoderm (spongy urethra)!
the ectoderm is going to continue to develop and form the prepuce around the penis and you’ll see the navicular fossa which is surface ectoderm.
What is Hypospadias?
occurring on the ventral surface of the penis, it’s an opening.
one of the most common defect in men.
What’s causing Glanular hypospadias?
what’s causing Penile Hypospadias?
What’s causing Penoscrotal Hypospadias?
incomplete closure of the urogenital (urethral) folds or problem with the navicular fossa.
incomplete closure of the urogenital folds
lack of fusion of the labioscrotal swellings (opening on scrotum)
Epispadias?
what’s causing it?
DORSAL surface.
opening on dorsal side.
improper location of genital tubercles to cloacal membrane
associated with estrophy of the bladder.
What are the different ovary ligaments?
suspensory ligament (coming from mesoderm)
Ovarian ligament (cranial part of the gubernaculum)
uterus ligaments?
Caudal part of the gubernaculum –> round ligament of the uterus
fusion of the paramesonephric ducts –> Broad ligament of the uterus!
What happens once you have the broad ligament formed?
you now separate the pelvic cavity, have a rectouterine pouch and vesico-uterine pouch
