T2 L12 Sexual Differentiation

Question 1

What is the prevalence of genital abnormalities?

Answer 1

1 in 4500

Question 2

What are the 3 main events involved in making a boy/girl?

Answer 2

1) Sex determination during fertilisation
2) Differentiation of gonads in week 5
3) Differentiation of internal and external genital organs after week 5

Question 3

When is sex determined?

Answer 3

At fertilisation

Question 4

What determines sex?

Answer 4

Inheritance of X/Y from father

Question 5

What happens at week 2?

Answer 5

Primordial germ cells arise from the epiblast

Question 6

What happens to the primordial germ cells?

Answer 6

They migrate to the yolk sac stalk to avoid becoming imprinted
Later return, travelling to genital ridge (next to kidney) and become indifferent gonad

Question 7

What happens to PGC at the genital ridge?

Answer 7

XX PGCs replicate at the cortex

XY PGCs replicate at the medulla

Question 8

What does gonad gender decision rely on?

Answer 8

Genetic switches

Hormones

Question 9

What are the 3 types of genetic switches?

Answer 9

General transcription factors (Wt1, Sf1)
Specific promoters of testis development (Sry, Sox9)
Specific promoters of ovarian development (Wnt-4, FoxL2)

Question 10

Describe the fate of female PGCs

Answer 10

Female PGCs become oogonia

Question 11

Describe the fate of sex cord cells

Answer 11

Become granulose which support and nitrify ovum

Question 12

Describe the fate of the cortex

Answer 12

Become layer of theca cells to secrete androgens before those generated by the follicles

Question 13

Describe the fate of male PGCs

Answer 13

Become spermatogonia

Question 14

What does AMH do?

Answer 14

Suppresses female development pathway

Induce cells in intermediate mesoderm to become leydig which then secrete testosterone

Question 15

Where is the origin of kidney development?

Answer 15

Intermediate mesoderm (reproductive organs also develop here)

Question 16

Where do the kidneys develop from?

Answer 16

Between somites and lateral plate (each side of aorta)

Question 17

What are the 3 stages of kidney development?

Answer 17

1) Pronephros
2) Mesonephros
3) Metanephros

Question 18

What are the 2 sets of paired ducts possessed by embryos of both sexes?

Answer 18

Paramesonephric - Mullerian

Mesonephric - Wolffian

Question 19

What does the Mullerian duct become in the female embryo?

Answer 19

Oviduct
Uterus
Cervix
Upper part of vagina

Question 20

What promotes Wolffian duct differentiation in the male?

Answer 20

Epididymis
Vas deferens
Seminal vesicle

Question 21

What does the genital tubercle consist of?

Answer 21

Urethral groove
Paired urethral folds
Paired labioscrotal swellings

Question 22

What does DHT stimulate the development of during male development?

Answer 22

Urethra
Prostate
External genitals (scrotum and penis)

Question 23

What does the genital tubercle become in the male?

Answer 23

Penis

Question 24

In the male, what forms the spongy urethra?

Answer 24

Fusion of urethral folds

Question 25

What forms the scrotum?

Answer 25

Labioscrotal swellings

Question 26

What does the genital tubercle become in the female?

Answer 26

Clitoris

Question 27

What forms the labia minor?

Answer 27

Urethral folds remain open

Question 28

What becomes the labia major?

Answer 28

Labioscrotal swellings

Question 29

What forms the vestibule?

Answer 29

Urethral groove

Question 30

What kinds of abnormalities can occur?

Answer 30

``` Chromosomal Hermaphroditism Gonadal dysfunction Tract abnormalities Gonadal descent External genitalia ```

Question 31

Give an example of a chromosomal condition

Answer 31

Turner's syndrome | Klinefelter's syndrome

Question 32

What is Turner's syndrome?

Answer 32

Monosomy XO 99% non-viable embryos Survivors fail to sexually mature at puberty Exhibit several physical abnormalities Diagnosis confirmed through amniocentesis

Question 33

How frequent is Turner's syndrome?

Answer 33

1 in 2500 females

Question 34

Symptoms of Turner's syndrome?

Answer 34

``` Short stature Low hairline Shield-shaped thorax Widely spaced nipples Shortened metacarpal IV Small finger nails Brown spots Characteristic facial features Fold of skin Constriction of aorta Poor breast development Elbow deformity Rudimentary ovaries No menstruation ```

Question 35

What is Klinefelter's syndrome?

Answer 35

47, XXY Birth appear normal Become infertile Exhibit some features associated with female development e.g. gynaecomastia Diagnosis confirmed through amniocentesis

Question 36

How common is Klinefelter's syndrome?

Answer 36

1:600-1000 male births

Question 37

Symptoms of Klinefelter's syndrome

Answer 37

``` Taller than average height Reduced facial hair Reduced body hair Breast development Osteoporosis Feminine fat distribution Small testes ```

Question 38

What is hermaphroditism?

Answer 38

Condition of having male and female reproductive organs

Question 39

What are true hermaphrodites?

Answer 39

Extremely rare Born with both ovarian and testicular tissue (ovotestis) 46 XX (Sry+), 45X (Sry+) & 45X External genitals may be ambiguous or appear to be female or male

Question 40

What is the possible cause of true hermaphrodites?

Answer 40

Two ova fertilised by 2 sperm that fuse to form a tetragamtic chimera

Question 41

What are female pseudohermaphrodite?

Answer 41

46 XX with virilisation due to androgens Internal sex organs are normal, including ovaries External appearance and genitals: male Features: fusion of labia, enlarged clitoris

Question 42

What are the causes of female pseudohermaphrodite?

Answer 42

Exposure to male hormones prior to birth e.g. from congenital virilising adrenal hyperplasia

Question 43

What are male pseudohermaphrodite?

Answer 43

46 XY with undervirilisation External genitals: incompletely formed, ambiguous or clearly female Some features: blind-ending vagina, absence of breast development, primary amenorrhoea Testis: normal, malformed or absent

Question 44

What are the main causes of male pseudohermaphrodite?

Answer 44

Defective androgen synthesis | Defective androgen action e.g. receptor disorder

Question 45

What is androgen insensitivity syndrome (AIS)?

Answer 45

Testicular feminisation Affects 1 in 20000-64000 male births (Male) hormones are normal Dysfunctional receptor to these hormones

Question 46

What is leydig cell hypoplasia?

Answer 46

Leydig cells don't secrete testosterone Possible reason: body insensitive to LH External genitalia: normally female / slightly ambiguous No female internal genitalia (uterus) develops

Question 47

Describe gonadal dysfunction?

Answer 47

Example: XY gonadal dysgenesis (Swyer's syndrome) Associated with XY karyotype Cause: alteration to Sry gene External appearance: female (no menstruation) No functional gonads (no testicular differentiation) Gonad may develop into malignancy

Question 48

Give some examples of tract abnormalities

Answer 48

Uterine e.g. unicornuate uterus Vagina e.g. agenesis Ductus deferens: unilateral or bilateral absence, failure of mesonephric duct to differentiate

Question 49

Describe cryptorchidism

Answer 49

May be unilateral / bilateral Occurs 30% premature, 3-4% term males Descent may occur during year 1

Question 50

Describe undescended ovaries

Answer 50

Quite rare | Detected in clinical fertility assessment

Question 51

What is the most common cause of abnormal external genitalia?

Answer 51

Male hypospadia 1 in 125 live male births Failure of male urogenital folds to fuse Outcome: proximally displaced urethral meatus