Embryo +CAH Flashcards
Wilms tumor related gene (WT-1)
Expressed in the developing genital ridge, kidney, and gonads.
WT-1 deletion/mut assoc. w/ gonadal dysgenesis and predilection for Wilms tumor and nephropathy
If there is a mutation or deletion in this gene, gonads dont develop or develop incorrectly.
NR5A1
aka steroidogenic factor (SF-1)
Regulates transcription of genes involved in gonadal and adrenal development, steroidogenesis, and reproduction.
SF-1 deletions can cause gonadal dysgenesis, adrenal failure, and persistent mullerian structures.
Where do germ cells form? Where do they migrate? What happens if they do not migrate?
In yolk sac
Germ cell migrate from the YOLK SAC and invade GENITAL RIDGE in 6th week.
If germ cells do not migrate, gonads, do not develop.
How do the primitive sex cords form?
Shortly before and during arrival of primordial germ cells, the epithelium of the genital ridge proliferates.
Epithelial cells then penetrate underlying mesenchyme, forming the primitive sex cords.
*next steps require expression of SRY
Expression of SRY at ____ weeks, leads to _____.
6 weeks
expression of SRY leads to gonads differentiating into testes.
- Primitive sex cords continue to proliferate and penetrate deep into medulla to form the testis or medullary cords
- Migration of mesonephric cells into developing testis
- Differentiation of sertoli cells and differentiation of leydig cells.
*recall SRY activates SOX9 which activates FGF9 and maintains positive loop to maintain SOX9 expression and testis formation.
sry
SRY activates SOX9 which activates FGF9 and maintains positive loop to maintain SOX9 expression and testis formation.
DAX-1
in double dose is responsible for anti-testis devel . . .
SOX-9
target of SRY
Essential for normal testis formation
With SF-1, elevates AMH concentrations
- AMH promotes regression of mullerian structures
Deletions or mut –> camptomelic dysplasia
- severe skeletal dysplasia
- gonadal dysgenesis in 75%
Testis cords are responsible for what?
At hilum, testis cords form rete testis
A dense layer of fibrous connective tissue (tunica albuginea), and separates the testis cords from the surface epithelium.
Testis cords are now composed of PGC’s and Sertoli cells.
Leydig cells lie between testis cords and begin Testosterone prod. by 8th week.
Genes imp in ovarian and follicular development
- DAX-1 (double dose)
- WNT-4
- RSPO1
- FOXL2
Cortex develops into ovaries and medulla fades away
Initially what two internal ducts develop in both sexes?
Mesonephric (wollfian) and
Paramesonephric (Mullerian)
Internal male ducts develop at what time?
begins at 8 weeks
What do the wolffian ducts diff into?
- EPididymis
- Vas deferens (ductus def)
- Seminal vesicles
Male internal ducts require what to continue its differentiation?
Process requires testicular secretions
- High local [testosterone]
- prod by leydig cells - Antimullerian hormone (AMH)
- prod by sertoli cells
- induces mullerian duct regression
- must be expressed before the end of the 8th week in the hu fetus
Female internal ducts require what to continue its differentiation?
Requires ABSENCE of local testosterone and AMH (opp of males)
Paramesonephric or mullerian ducts form what eventually?
- Fallopian tubes
- Midline uterus
- Upper portion of vagina
- Wolffian ducts regress
Rokitansky syndrome aka Mullerian agenesis (567)
absent or underdeveloped mullerian structures (uterus, vagina) in a 46 XX female
female will present with primary ammenorrhea
- will get breast devel. + pubic hair (ovary working)
*presentation varies greatly
Persistent mullerian ducts in 46 XY
Present with unilateral hernia
- will find mullerian ducts during surgery
Due to defect in AMH synthesis or AMH receptor
*recall that AMH promotes regression of mullerian structures
External genitalia develops from what 3 indifferent structures?
- Genital tubercle –>
gland penis or clitoris - Urethral folds –>
urethra or labia minora - Labial-scrotal (genital) swelling –>
scrotum or labia majora
Male external genitalia are dependent on what?
Testosterone and especially DHT
- T is converted to DHT by 5-a reductase
- DHT has higher receptor affinity than T
*DHT needed for penile growth and formation of penile urethra
In first trimester, what stimulates leydig cells to make T?
What about after 1st trimester?
1st: placental HCG stimulates leydig cells to make T
- remember HCG is like LH (stim LH recept)
after 1st: hypothalamic pituitary testicular axis required for continued T prod.
Male external genitalia are complete by ____
13 weeks
- so any defects that occur befre 13 weeks of age cannot be corrected by subsequent androgen exposure (can only make it bigger)
Testis descend and reach inguinal region by ____ and scrotum by _____ (time).
What occurs if there is failure to reach scrotal sac?
12 weeks
33 weeks
Crytorchidism
Three components to psychosocial dev.
- Gender identity
- identify as Male or Female - Gender role
- behavior (defined by culture) - Sexual orientation
- may not be black in white, and may not be in same dir.
- ie: androgen insensitivity: more likely to identify as females but more like to have male gender roles
