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203 - Theme 2 - Reproductive System, Fetal Development, Pregnancy and Birth > L11 Sexual differentiation > Flashcards

L11 Sexual differentiation Flashcards

1
Q

Prevalence of genital abnormalities

A

1 in 4500

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2
Q

3 main events in sexual differentiation

A

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

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3
Q

Sex determination (2)

A

Sex is determined at fertilisation

Inheritance of X/Y from father

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4
Q

Gonad origin and differentiation (5)

A

At week 2 primordial germ cells (PGCs) arise from the epiblast

PGCs are pluripotent

PGCs migrate to yolk sac stalk to avoid becoming imprinted

Later return, travelling to the genital ridge (next to kidney) and become the indifferent gonad

At genital ridge: XX PGCs replicate at cortex; XY PGCs replicate at the medulla

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5
Q

Gonad gender decision relies on? (2)

A

Genetic switches

Hormones

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6
Q

Genetic switches (3)

A

General transcription factors
e.g. Wt1, Sf1

Specific promoters of testis development
e.g. Sry, Sox9

Specific promoters of ovarian development
e.g. Went-4, FoxL2

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7
Q

Fate of gonadal cells in females (3)

A

Female PGCs => oogonia (primary oocytes)

Sex cord cells => granulosa (support and nutrifying the ovum)

Cortex => layer of thecal cells => secrete androgens before those generated by the follicles

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8
Q

Fate of gonadal cell lines in males (4)

A

Male PGCs => spermatogonia

Sry influences definition + identity of Sertoli cells => secretion of AMH

AMH surpasses female development pathway

AMH induce cells in intermediate mesoderm to become Leydig => secrete testosterone

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9
Q

Kidney development: origin

A

Intermediate mesoderm (as the reproductive organs)

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10
Q

Kidney development: where

A

Between the somites and lateral plate (each side of the aorta)

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11
Q

Kidney development: 3 stages

A

Pronephros - disappears soon after

Mesonephros - leaves remnants, leaves behind ducts that become integral part of the reproductive system

Metanephros - becomes kidney

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12
Q

Internal genital organs

A

Begin differentiation at about week 8 formed from a priori identical primordium structures i.e.

embryos of both sexes possess two sets of paired ducts at the start:

  • paramesoneohric aka Mullerian
  • mesonephric aka Wolffian
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13
Q

Internal genital organs: female

A

In female embryo: Mullerian duct is kept due to the absence of AMH

Mullerian duct

  • oviduct
  • uterus
  • cervix
  • upper part of the vagina
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14
Q

Internal genital organs: males

A

In male embryo:

  • AMH causes Mullerian duct regression
  • Testosterone promotes Wolffian duct differentiation

Wolffian duct

  • Epididymis
  • Vas deferens
  • Seminal vesicle
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15
Q

External genital organs

A

At first embryos of both sexes show an elevated midline swelling - genital tubercle

Tubercle consists:

  • urethral groove (opening into the urogenital sinus)
  • paired urethral folds
  • paired labioscrotal swellings
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16
Q

External genital organs: Male

A

Some testosterone is converted into dihydrotestosterone (DHT)

DHT stimulates development of the urethra, prostate and external finites (scrotum and penis)

Genital tubercle => penis

Fusion of the urethral folds => spongy urethra

Labioscrotal swellings => scrotum

17
Q

External genital organs: female

A

Absence of DHT

Genital tubercle => clitoris

Urethral folds remain open => labia minor

Labioscrotal swellings => labia majora

Urethral groove => vestibule

18
Q

Types of abnormalities (6)

A

Chromosomal

Hermaphroditism

Gonadal dysfunction

Tract abnormalities

Gonadal descent

External genitalia

19
Q

Chromosomal: Turner’s syndrome

A

Monosomy, XO

1:2500 female (does not affect males)

99% non-viable embryos

Survivors fail to sexually mature at puberty

Exhibit several physical abnormalities

Diagnosis confirmed through amniocentesis

20
Q

Physical abnormalities in Turner’s syndrome

A

Short stature

Low hairline

Widely spaced nipples

Poor breast development

Brown spots (nevi)

Constriction of aorta

21
Q

Chromosomal: Klinefelter’s syndrome

A

47, XXY

1:600 - 1000 male births (does not affect females)

Birth appear normal (undetected)

Become infertile

Exhibit some features associated with female development (e.g. gynaecomastia)

Diagnosis confirmed through amniocentesis

22
Q

Physical abnormalities in Klinefelter’s Syndrome

A

Taller than average height

Reduced facial hair

Reduced body hair

Breast development

Osteoporosis

Feminine fat distribution

Small testes

23
Q

Hermaphroditism

A

Named after the offspring of the Greek gods Hermes and Aphrodite

True hermaphrodite

Female pseudohermaphrodite

Male pseudohermaphrodite

24
Q

True hermaphrodite

A

Extremely rare

Born with both ovarian and testicular tissue (ovotestis)

46XX (SRY+), 45X (SRY+) and 45X

Possible cause e.g. two ova fertilised by two sperm that fuse to form a tetragametic chimera

External genitals may be ambiguous, or appear to be female or male

25
Q

Female pseudohermaphrodite

A

46, XX with virilisation (due to androgens)

Internal sex organs are normal, inc. ovaries

External appearance and genitals: male

Features: fusion of labia; enlarged clitoris

Possible cause: exposure to male hormones prior to birth (e.g. from congenital virilising adrenal hyperplasia)

26
Q

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 amenorrhea

Testis: normal, malformed or absent

Main causes:

  • defective androgen synthesis
  • defective androgen action (e.g. receptor disorder)
27
Q

Male pseudohermaphrodite: AIS

A

Androgen Insensitivity Syndrome

Aka testicular feminisation

Affects: 1:20000-64000 male births

Male hormones are normal

Dysfunctional receptor to these hormones

28
Q

Male pseudohermaphrodite: Leydig cell hypoplasia

A

Lydia cells do not secrete testosterone

Possible reason: body insensitive to LH

External genitalia normally female/slightly ambiguous

No female internal genitalia (uterus) develops

29
Q

Gonasal dysfunction

A

E.G. XY gonadal dysgenesis aka 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

30
Q

Some examples of tract abnormalities

A

Uterine e.g. unicornuate uterus

Vagina e.g. genesis

Ductus Deferens: unilateral or bilateral absence, failure of mesonephric duct to differentiate

31
Q

Gonadal descent

A

More apparent and common in males (cryptorchidism) than on females (undescended ovaries)

32
Q

Cryptorchidism

A

May be unilateral/bilateral

Occurs 30% premature; 3-4% term males

Descent may take place during year 1

33
Q

Undescended ovaries

A

Quite rare

Detected in clinical fertility assessment

34
Q

External genitalia

A

Most common: male hypospadia

1:125 live male births

Failure of male urogenital folds to fuse

Outcome: proximally displaced urethral meatus

35
Q

The brain and behaviour

A

What also makes us a girl or a boy: sexual behaviour

Research released brain acquires ‘gender identity’ not for influence of sex hormones but instead from gene expression

Gees active before gonads even develop, week 2

203 - Theme 2 - Reproductive System, Fetal Development, Pregnancy and Birth (17 decks)

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