Sexual Differentiation

Question 1

What’s the difference between Sexual DETERMINATION and DIFFERENTIATION?

What is Gonadal sex dependent on?

In which gestational week does this gene switch on?

What hormones do the Testes produce?

Answer 1

• • Sexual determination is a genetically controlled process dependent on Y chromosome
  • Sexual differentiation is the development of internal and external genitalia
• Sex Determining Region (SRY) gene, which forms the Testes
• From Week 7
• Anti-Mullerian Hormone (AMH) and Testosterone

Question 2

What’s a way to describe the gonads during very early pregnancy? What does this mean?

Where does the Genital ridge Primordia form?

Answer 2

• Bipotential = Can become testes or ovaries

- Posterior wall of the Lower Thoracic/Lumbar region

Question 3

GENITAL RIDGE CELL TYPES:
Primordial Germ cells:
What cells do these become?

How does it develop? When by?

Where do they migrate? When by?

Primitive Sex Cords:
What cells do these become?

What do Sertoli cells produce?

How do they migrate?

How do they differ in Males and Females?

Mesonephric cells:
What cells do these become?

What do Leydig cells produce?

In Males, what are these cells under the influence of? What does this influence express?

In Males, what does it form?

Answer 3

• Sperm or Oocytes
• From Yolk sac epithelium and expands by mitosis by Week 3
• Migrates to Hindgut connective tissue, Kidneys and Genital ridge by Week 6

• SERTOLI cells (Male) or GRANULOSA cells (Female)
• AMH
• Migrates inwards as Columns
• • Males; Express SRY, Surrounds primordial germ cells to form Testis cords
  • Females; No SRY expression, Condenses around cortex as clusters

• LEYDIG cells (Male) or THECA cells (Female)
• Testosterone
• Pre-Sertoli cells, which express SRY
• Rete-testis and Seminiferous tubules

Question 4

Internal Reproductive Organs:
Which ducts are involved in Females?

What do these form?

What are they inhibited by?

Which ducts are involved in Males?

What do these form?

What are they stimulated by?

What are they inhibited by?

External Reproductive Organs:
What is the main hormone in the development of this? What is it produced from and which enzyme is involved?

How is DHT’s binding efficacy compared to Testosterone?

What does DHT cause? What are the physical changes that occur?

Answer 4

• Mullerian ducts
• Uterine tubes, Uterus, and Upper 1/3 of Vagina
• Inhibited in males by AMH (from Sertoli cells)
• Wolffian ducts
• Epididymis, Vas Deferens, Seminal vesicles, and Ejaculatory ducts
• Testosterone
• Inhibited in females by a LACK OF Testosterone (from Leydig cells)

• DHT (Dihydrotestosterone); Testosterone is converted into DHT by 5-α-REDUCTASE
• Binds to testosterone receptors, but with ↑Efficacy (↑POTENT)
• Differentiation of Male EXTERNAL genitalia
  o Clitoral area enlarges into Penis
  o Labia fuse and become rugged to form Scrotum
  o Prostate forms

Question 5

What is Gonadal Dysgenesis? What is this due to?

What is Sex Reversal?

What is Intersex?

Answer 5

• Incomplete differentiation, usually due to missing SRY in male or partial/complete deletion of the second X chromosome in female
• Phenotype doesn’t match Genotype
• Components of both tracts or Ambiguous genitalia

Question 6

ANDROGEN INSENSITIVITY SYNDROME (AIS):
What is it?

Complete AIS:
How does it appear at birth?

What do Bloods and an USS show?

What are the 2 main symptoms?

Partial AIS:
What can it vary between?

Answer 6

• XY individual with Testosterone production (Leydig), but Receptor resistance
• Look female at birth, but with undescended Testes
• Bloods show male levels of Androgens, USS shows Testes
• Primary Amenorrhoea, Lack of body hair
• Ambiguous genitalia to a Large Clitoris

Question 7

5-α-REDUCTASE DEFICIENCY:
What is it?

What type of condition is it?

How does it present?

If not diagnosed at birth, when does it become very apparent? Why?

Answer 7

• XY individual with Testosterone production (Leydig), but no conversion to DHT
• Autosomal Recessive
• Has all of the male Internal genitalia, but the lack of DHT leads to an underdeveloped External Genitalia (Appear female or have ambiguous genitalia)
• During Adrenarche and Puberty because of Virilisation due to High Testosterone levels

Question 8

TURNER SYNDROME:
What is it?

What are the signs and symptoms?

Answer 8

• 45XO individual (No Y chromosome) - Failure of Ovarian function
• o ‘STREAK’ OVARIES = Ovarian dysgenesis occurs as 2X chromosomes are needed for ovarian development
  o Small Uterus, Uterine tubes, and other defects in growth

Question 9

CONGENITAL ADRENAL HYPERPLASIA (CAH):
What is it?

What appears at birth?

How is Aldosterone affected? What does lead to?

How is Cortisol affected? How is this treated?

Answer 9

• XX individual exposed to high levels of androgens
• Wrong gender assigned at birth, or Ambiguous genitalia
• ↓Aldosterone = Salt-wasting = Hypotension and Hyperkalaemia
• ↓Cortisol = Reduced negative feedback, with an ↑Androgen level
  o Treated with Glucocorticoids to correct the loss of negative feedback