Embryo +CAH

Question 1

Wilms tumor related gene (WT-1)

Answer 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.

Question 2

NR5A1

Answer 2

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.

Question 3

Where do germ cells form? Where do they migrate? What happens if they do not migrate?

Answer 3

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.

Question 4

How do the primitive sex cords form?

Answer 4

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

Question 5

Expression of SRY at ____ weeks, leads to _____.

Answer 5

6 weeks

expression of SRY leads to gonads differentiating into testes.

1. Primitive sex cords continue to proliferate and penetrate deep into medulla to form the testis or medullary cords
2. Migration of mesonephric cells into developing testis
3. 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.

Question 6

sry

Answer 6

SRY activates SOX9 which activates FGF9 and maintains positive loop to maintain SOX9 expression and testis formation.

Question 7

DAX-1

Answer 7

in double dose is responsible for anti-testis devel . . .

Question 8

SOX-9

Answer 8

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%

Question 9

Testis cords are responsible for what?

Answer 9

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.

Question 10

Genes imp in ovarian and follicular development

Answer 10

1. DAX-1 (double dose)
2. WNT-4
3. RSPO1
4. FOXL2

Cortex develops into ovaries and medulla fades away

Question 11

Initially what two internal ducts develop in both sexes?

Answer 11

Mesonephric (wollfian) and

Paramesonephric (Mullerian)

Question 12

Internal male ducts develop at what time?

Answer 12

begins at 8 weeks

Question 13

What do the wolffian ducts diff into?

Answer 13

1. EPididymis
2. Vas deferens (ductus def)
3. Seminal vesicles

Question 14

Male internal ducts require what to continue its differentiation?

Answer 14

Process requires testicular secretions

1. High local [testosterone]
   - prod by leydig cells
2. 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

Question 15

Female internal ducts require what to continue its differentiation?

Answer 15

Requires ABSENCE of local testosterone and AMH (opp of males)

Question 16

Paramesonephric or mullerian ducts form what eventually?

Answer 16

1. Fallopian tubes
2. Midline uterus
3. Upper portion of vagina

• Wolffian ducts regress

Question 17

Rokitansky syndrome aka Mullerian agenesis (567)

Answer 17

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

Question 18

Persistent mullerian ducts in 46 XY

Answer 18

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

Question 19

External genitalia develops from what 3 indifferent structures?

Answer 19

1. Genital tubercle –>
   gland penis or clitoris
2. Urethral folds –>
   urethra or labia minora
3. Labial-scrotal (genital) swelling –>
   scrotum or labia majora

Question 20

Male external genitalia are dependent on what?

Answer 20

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

Question 21

In first trimester, what stimulates leydig cells to make T?

What about after 1st trimester?

Answer 21

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.

Question 22

Male external genitalia are complete by ____

Answer 22

13 weeks

• so any defects that occur befre 13 weeks of age cannot be corrected by subsequent androgen exposure (can only make it bigger)

Question 23

Testis descend and reach inguinal region by ____ and scrotum by _____ (time).
What occurs if there is failure to reach scrotal sac?

Answer 23

12 weeks

33 weeks

Crytorchidism

Question 24

Three components to psychosocial dev.

Answer 24

1. Gender identity
   - identify as Male or Female
2. Gender role
   - behavior (defined by culture)
3. 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

Question 25

Role of fetal exposure to androgens:
46XX CAH
46XY w/ cloacal extrophy

Answer 25

46XX CAH: male gender role behavior in childhood

46XY w/ cloacal extrophy raised as girls have high rate of gender dysphoria
*have a little nub as penis

Question 26

Key to sexual dimorphism is on which chromosome

- what is it, what is its fxn?

Answer 26

Y chromosome

• SRY (sex determining region of Y)
• protein transcription factor which activates other txn factors and intitates testicular differentiation from indifferent gonads

Question 27

Undifferentiated gonads first appears at _____ weeks as ____. Describe this process.

Answer 27

4-5 weeks as paired genital ridges

Genital ridges form in the posterior abdominal wall, just medial to the developing mesonephros.

Formed from proliferation of the epithelium and condensation of underlying mesenchyme

Question 28

Development of the indifferent gonad begins at the ______ week of gestation.

Answer 28

5th week of gestation

Question 29

what two transcription factors are expressed in the genital ridge and important for gonadal development?

Answer 29

WT-1 and NR5A1 (aka SF-1)

Question 30

By the 7th week, are the gonads still undifferentiated and bipotential?

Answer 30

yes

but starting at 7 weeks, expression of SRY initiates a genetic cascade that causes the indifferent gonad to develop into testes

Question 31

Rearrange order of Testicular development from earliest to latest:

• seminiferous tubules
• leydig cells
• spermatogenic cords

Answer 31

1. Spermatogenic cords
2. Seminiferous tubules
3. Leydig cells

Question 32

In the first trimester, ____ stimulates leydig cells and in the 2nd and 3rd trimester _____ stimulates the leydig cells to secrete testosterone.

Answer 32

hCG

fetal pituitary LH

Question 33

In the XX gonad, absence of SRY and expression of RSPO1 and WNT4 leads to _______.

Answer 33

formation of the ovary

Question 34

How many x chromosomes are necessary to maintain ovarian integrity?

Answer 34

2

Question 35

what would you expect if a female is exposed to excessive androgen exposure before 12 weeks gestation?

Answer 35

Can lead to posterior labial fusion and penile urethra with a urogenital sinus