Control of sex determination

Question 1

Outline Gonad formation

Answer 1

• The urogenital ridge divides into the nephrogenic ridge and the gonadal ridge
• The nephrogenic ridge develops into the mesonephric ducts or Wolffian ducts& the precursors of the urinary system
• The paramesonephric ducts or Mullerian ducts develop from further invagination of the intermediate mesoderm
• The primordial germ cells migrate to the gonadal ridge which develops into the gonads

Question 2

What drives testicular differentiation ?

Answer 2

-SRY expression

Question 3

Outline male sex differentiation

Answer 3

• Wolffian ducts persist-male internal reproductive organs
• Male external genitalia
• Development of male secondary sexual characteristics
• Spermatogenesis

Question 4

Outline female sex differentiation

Answer 4

• Mullerian ducts persist-female internal reproductive organs
• Female external genitalia
• Development of female secondary sexual characteristics
• Ovulation & fertility

Question 5

What does formation of the bipotential gonad depend on?

Answer 5

-A number of transcription factors

Question 6

Explain gonad determination

Answer 6

• Formation of the ovary/testes from the bipotential gonad
• The presence of a Y chromosome leads to testes formation
• likely to be a testes determining factor on the Y chromosome

Question 7

Outline the formation of the testes involving SOX9 and DAX1

Answer 7

SOX9:
-Gene on chromosome 17
-Acts on downstream targets to promote development of the testes 
-Dosage sensitive
DAX1 (orphan nuclear receptor)
-Gene on X chromosome 
-Represses testes development
-Dosage sensitive 
-Duplications lead to DSD in XY individuals

Question 8

What is the role of the anti-Mullerian hormone ( AMH) in Gonadal formation

Answer 8

• AMH leads to regression of the mullerian structures

- Testosterone promotes the development of the Wolffian duct into the epididmis, vas deferens and seminal vesicles

Question 9

What happens to testosterone in the presence of a testis?

Answer 9

• Testosterone is converted to the more potent androgen Dihydrotestosterone ( DHT)
• DHT promotes the development of the genital tubercles, labioscrotal folds& urogenital sinus into the penis, scrotum& prostate

Question 10

What occurs in the absence of AMH

Answer 10

• The Mullerian duct develops into the fallopian tubes, uterus& upper vagina (NOTE, NOT THE WHOLE OF THE VAGINA)
• The Wolffian duct regresses
• The genital tubercles, labioscrotal folds& urogenital sinus develop into the lower vagina, vulva clitoris
• These processes are not dependant on the presence of a functional ovary

Question 11

Which hormone is involved in Mullerian duct formation

Answer 11

Estrogen

Question 12

Is Wolffian duct regression active or passive

Answer 12

Passive

Question 13

If Mullerian duct regression active or passive

Answer 13

Active, involves AMH( which is produced by the testis)

Question 14

Outline Klinefelter syndrome

Answer 14

Karyotype, 47 XXY
Clinical features:
-Normal at birth, higher incidence of undescended testes
-Tall stature
-Small ‘pea-sized’ testes
-Lack of secondary sexual characteristics
-Gynaecomastia
-Infertility
-Some behavioural and minor learning disabilities

Question 15

What is the function of DAX1 in development of Klinefelter syndrome

Answer 15

• The factor DAX 1 is located on the X chromosome and is dosage sensitive
• Here there are 2 X chromosomes so the guy has 2 copies of DAX 1 and cos DAX 1 regresses the function of the SRY gene; that is why these problems result with Klinefelter’s syndrome

Question 16

How can DSDs arise from a region of a chromosome

Answer 16

• SRY translocations
• Chromosomally: still looks like XX but has this vital SRY gene on it so testis produced therefore testosterone and AMH are produced
• Present after puberty with short stature, gynaecomastia, small testes, fertility issues
• Male gender indentity
• Treated with testosterone

Question 17

How can disorders of sexual development ( DSDs) arise?

Answer 17

From variation at the level of:

• A whole chromosome
• The region of a chromosome
• A change within a single gene

Question 18

How can DSDs arise from a change within a single gene ?

Answer 18

• 5 alpha reductase deficiency. This is the enzyme involved in the conversion from testosterone to the male potent androgen DHT
• Internal structures male
• Variable appearance of external genitalia at birth
• During puberty increased androgen levels lead to virilisation of external genitalia
• The tissues of external genitalia start to change around puberty
• Others may have genitalia that appear predominantly male, often with an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias).