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Module 203 Reproduction & endocrinology > T2 L12 Sexual Differentiation > Flashcards

T2 L12 Sexual Differentiation Flashcards

1
Q

What is the prevalence of genital abnormalities?

A

1 in 4500

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2
Q

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

A

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

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3
Q

When is sex determined?

A

At fertilisation

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4
Q

What determines sex?

A

Inheritance of X/Y from father

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5
Q

What happens at week 2?

A

Primordial germ cells arise from the epiblast

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6
Q

What happens to the primordial germ cells?

A

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

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7
Q

What happens to PGC at the genital ridge?

A

XX PGCs replicate at the cortex

XY PGCs replicate at the medulla

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8
Q

What does gonad gender decision rely on?

A

Genetic switches

Hormones

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9
Q

What are the 3 types of genetic switches?

A

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

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10
Q

Describe the fate of female PGCs

A

Female PGCs become oogonia

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11
Q

Describe the fate of sex cord cells

A

Become granulose which support and nitrify ovum

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12
Q

Describe the fate of the cortex

A

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

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13
Q

Describe the fate of male PGCs

A

Become spermatogonia

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14
Q

What does AMH do?

A

Suppresses female development pathway

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

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15
Q

Where is the origin of kidney development?

A

Intermediate mesoderm (reproductive organs also develop here)

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16
Q

Where do the kidneys develop from?

A

Between somites and lateral plate (each side of aorta)

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17
Q

What are the 3 stages of kidney development?

A

1) Pronephros
2) Mesonephros
3) Metanephros

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18
Q

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

A

Paramesonephric - Mullerian

Mesonephric - Wolffian

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19
Q

What does the Mullerian duct become in the female embryo?

A

Oviduct
Uterus
Cervix
Upper part of vagina

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20
Q

What promotes Wolffian duct differentiation in the male?

A

Epididymis
Vas deferens
Seminal vesicle

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21
Q

What does the genital tubercle consist of?

A

Urethral groove
Paired urethral folds
Paired labioscrotal swellings

22
Q

What does DHT stimulate the development of during male development?

A

Urethra
Prostate
External genitals (scrotum and penis)

23
Q

What does the genital tubercle become in the male?

A

Penis

24
Q

In the male, what forms the spongy urethra?

A

Fusion of urethral folds

25
Q

What forms the scrotum?

A

Labioscrotal swellings

26
Q

What does the genital tubercle become in the female?

A

Clitoris

27
Q

What forms the labia minor?

A

Urethral folds remain open

28
Q

What becomes the labia major?

A

Labioscrotal swellings

29
Q

What forms the vestibule?

A

Urethral groove

30
Q

What kinds of abnormalities can occur?

A 
Chromosomal
Hermaphroditism
Gonadal dysfunction
Tract abnormalities
Gonadal descent
External genitalia
31
Q

Give an example of a chromosomal condition

A

Turner’s syndrome

Klinefelter’s syndrome

32
Q

What is Turner’s syndrome?

A

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

33
Q

How frequent is Turner’s syndrome?

A

1 in 2500 females

34
Q

Symptoms of Turner’s syndrome?

A 
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
35
Q

What is Klinefelter’s syndrome?

A

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

36
Q

How common is Klinefelter’s syndrome?

A

1:600-1000 male births

37
Q

Symptoms of Klinefelter’s syndrome

A 
Taller than average height
Reduced facial hair
Reduced body hair
Breast development
Osteoporosis 
Feminine fat distribution
Small testes
38
Q

What is hermaphroditism?

A

Condition of having male and female reproductive organs

39
Q

What are true hermaphrodites?

A

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

40
Q

What is the possible cause of true hermaphrodites?

A

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

41
Q

What are female pseudohermaphrodite?

A

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

42
Q

What are the causes of female pseudohermaphrodite?

A

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

43
Q

What are male pseudohermaphrodite?

A

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

44
Q

What are the main causes of male pseudohermaphrodite?

A

Defective androgen synthesis

Defective androgen action e.g. receptor disorder

45
Q

What is androgen insensitivity syndrome (AIS)?

A

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

46
Q

What is leydig cell hypoplasia?

A

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

47
Q

Describe gonadal dysfunction?

A

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

48
Q

Give some examples of tract abnormalities

A

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

49
Q

Describe cryptorchidism

A

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

50
Q

Describe undescended ovaries

A

Quite rare

Detected in clinical fertility assessment

51
Q

What is the most common cause of abnormal external genitalia?

A

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

Module 203 Reproduction & endocrinology (52 decks)

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