sexual differentiation and disorders

Question 1

What is sexual differentiation?

Answer 1

process by which internal and external genitalia develop as male or female

Question 2

What initiates male sexual differentiation?

Answer 2

Sex determining region (SRY) gene on short arm of Y chromosome, acting as a transcription factor

Question 3

Presence of SRY causes development of…

Answer 3

testis

Question 4

Absence of SRY causes development of…

Answer 4

ovaries

Question 5

What cells do testis develop?

Answer 5

Sertoli cells: produce AMH

Leydig cells: produce testosterone

Question 6

What are Genital ridges?

Answer 6

bipotential cluster of cells in embryo
-can develop either testis or ovaries which are responsible for the differentiation of primordial germ cells into male/female gametes

Question 7

What are the Cells invading genital ridge?

Answer 7

1) Primordial Germ Cells: become sperm or oocytes
2) Primitive Sex Cords: become Sertoli cells or Granulosa cells
3) Mesonephric Cells: become Leydig cells or Theca cells; also blood vessels

Question 8

Describe the Action of primitive sex cords in males and females.

Answer 8

penetrate medullary mesenchyme deeply to form testis cords, which then become Sertoili cells in males

ill defined in females, therefore don’t penetrate deeply and condense in cortex around primordial germ cells to become Granulosa cells

Question 9

What are Mullerian Ducts?

Answer 9

Embryonic ducts that can develop into female internal genitalia

Question 10

What are Wolffian Ducts?

Answer 10

Embryonic ducts that can develop into male internal genitalia under stimulation by testosterone

Question 11

How do males not develop mullerian ducts?

Answer 11

Mullerian ducts are inhibited by AMH (produced by Sertoli cells), hence they are regressed in males

Question 12

How do females not develop Wolffian ducts?

Answer 12

Lack of stimulation by testosterone causes regression of Wolffian ducts in femlaes

Question 13

What is external genitalia development influenced by?

Answer 13

Testosterone and dihydrotestosterone (DHT)

Question 14

What is 5 alpha Reductase?

Answer 14

an enzyme that converts testosterone into dihydrotestosterone

• in genital skin
• present in both males and females

Question 15

Describe the Male external differentiation

Answer 15

Conversion of testosterone to DHT by 5a Reductase:

• genital tubercle swells and becomes glans penis
• genital swelling swells up more to become scrotal swelling and then scrotum
• testes descend through inguinal canal into scrotum
• scrotum skin becomes ruggated
• urethral fold folds around urogenital membrane and becomes tube

Question 16

Describe the Female external differentiation?.

Answer 16

5a Reductase present, but no testosterone, therefore no DHT produced, causing:

• genital tubercle becomes clitoris
• genital swellings enlarge and form labia majora
• urethral fold develops in labia minora
• urogenital membranes forms vestibule of vagina

Question 17

What is Androgen Insensitivity Syndrome (AIS)?

Answer 17

A syndrome caused by a mutation of the androgen receptor gene that renders tissues insensitive to androgenic hormones like testosterone.

Affected XY individuals:

• external female genitalia due to absence of DHT
• testis form due to SRY gene presence
• regressed internal genitalia because AMH inhibit Mullerian ducts and no testosterone stimulation for Wolffian duct differentiation

Question 18

What is 5-Alpha Reductase Deficiency?

Answer 18

Testosterone in XY individual can’t be converted to DHT:

• testes form due to SRY gene
• internal male genitalia due to AMH inhibiting Mullerian Ducts and stimulation of Wolffian Ducts by testosterone
• external female genitalia because no DHT

Question 19

What is Turner Syndrome?

Answer 19

Female genetic condition with one X chromosome (XO)

• ovaries develop (no SRY gene)
• Internal female genitalia because no AMH for Mullerian duct development and lack of testosterone prevents Wolffian duct differentiation
• external female genitalia

Question 20

What is the Effect of one X chromosome (Turner Syndrome) on ovaries?

Answer 20

Ovarian dysgenesis (streak ovaries)

Question 21

What is Congenital Adrenal Hyperplasia?

Answer 21

XX female exposed to high levels of androgens in utero

Progestogens (in gonads) can be converted to cortisol and aldosterone (in adrenal glands) by 21a hydroxylase

Defect/Deficiency in 21a hydroxylase causes:

• no cortisol/aldosterone produced therefore more progestogens
• no negative feedback via HPA axis, increase in CRH and ACTH
• ACTH upregulates P40scc enzyme to force more cholesterol into steroid synthesis pathway
• progestogens converted to androgens (high testosterone)

> Internal female genitalia (no AMH) development of Mullerian ducts

> not internal male genitalia because androgen levels not high enough to rescue Wolffian ducts

• external male genitalia (high DHT)
• PHIV