Normal Sexual Differentiation

Question 1

Define sexual determination

Answer 1

Genetically controlled process which is dependant on the switch on the Y chromosome.

Determines male /female on chromosomal level

Question 2

Define Sexual differentiation

Answer 2

This is the process by which internal and external genitalia will develop as male or female

Question 3

What gene determines the development of male gonads?

Answer 3

The SRY gene

Question 4

What does the presence of the SRY gene determine ?

Answer 4

The SRY gene will lead to testis determination.

This is switched on briefly during embryo development and makes gonad into testis.

Question 5

What will happen when there is no SRY gene ?

Answer 5

This will cause the development of ovaries

Question 6

Define gonadal sex

Answer 6

This is defined as the sex as determined on the basis of the gonadal tissue present

(Ovary vs Testis )

Question 7

What are the hormones made in the Testis and what cells secrete them ?

Answer 7

Sertoli cells - AMH (Anti-Mullerian hormone )

Leydig cells - Testosterone

Question 8

What is Euchromatin ?

Answer 8

This is lightly packed form which is enriched

Question 9

How does the SRY gene act as a transcription factor ?

Answer 9

It is a gene for a transcription factor which binds to the DNA on other chromosomes causing genes to be transcribed which also act as transcription factors which leads to a cascade signalling to make a testis which will then lead to hormone production which triggers secual differentiation.

Question 10

What is heterochromatin ?

Answer 10

This is tightly packed form of DNA which is condensed and inactive for transcription.

Question 11

What is the affect of the AMH hormone ?

Answer 11

This stops the development of the Mullerian duct in males

Question 12

What is the critical site of DNA binding involved with the SRY gene ?

Answer 12

This is found upstream to the SOX9 gene which is also a transcription factor

Question 13

Outline the mechanism of the SOX9

Answer 13

SOX9 is a transcription factor which can bind to its own upstream activation site which means it can cause a positive feedback loop.
This means SOX9 levels remain high even in absence of SRY.

SOX9 acts to stimulate the expression of further downstream genes

Question 14

How does SOX9 work?

Answer 14

SOX9 works by keeping ovarian genes off , swithcing on testicular genes and keeping these on.

This causes the development of male gonads/genitalia

Question 15

How does SOX9 achieve its effects ?

Answer 15

1.Stimulates prostaglandin D2 production (PGD2) through pre-Sertoli cells.
This acts as paracrine hormone and stimulates further SOX9 production,
Positive feedback loop re-enforced precursor cells along Sertoli pathway’s

2.Stimulates production of fibroblast growth factor 9 (FGF9).FGF9 will then act as a chemotactic factor for cell migration into developing testis. Also further stimulates production of SoX9 (further positive feedback)

3.Sox9 stimulates production of AMH.
AMH causes the regression of Mullerian ducts which develop into uterus and fallopian tubes in female.

4.Inhibition of female transcription factors WNT4 /FOXL2
(These are required in the female cascade to become a female )

Question 16

What would the Mullerian duct develop into in the absence of AMH ?

Answer 16

The fallopian tube and the uterus

internal female genitalia

Question 17

Describe the early stage of gonad development

Answer 17

During this stage the pair of gonads is bipotential which means they can give rise to male /female genitalia .

The pre cursor is derived from common somatic mesenchymal tissue precursors called the genital ridge primordia on the posterior wall of lower thoracic lumbar region.

The genital ridges could become pair of ovaries or testes

Question 18

Outline the development process of the genital ridge

Answer 18

Three waves of cells will invade the genital ridge :

Primordial Germ Cells -Sperm/Oocyte

Primitive sex chords -Sertoli cells,Granulosa cells

Mesonephric cells =Blood vessels , Theca /Leydig cells

Question 19

What is the process of primordial germ cell migration?

Answer 19

Initial cluster of cells in epithelium of yolk sac expand through mitosis at 3 weeks

Migrate to connective tissue of hind gut , developing kidney area and genital ridge (takes 6 weeks )

Question 20

What is the process primitive sex cord migration in female ?

Answer 20

Female =No SRY

Ill defined sex cords , do not penetrate deeply but instead condense in the cortex as small clusters around primordial germ cells = precursor of ovarian follicle

This forms Granulosa cells

Question 21

What is the process of primitive sex cord migration in males?

Answer 21

Male=SRY expression

Penetrate the medullary mesenchyme and surround
primordial germ cells to form testis cords -precursors of seminiferous tubules

Sertoli cells which will express AMH .

Question 22

Define Mesonephric cells and where they come from

Answer 22

These originate in the mesonephric primordium which is found lateral (sideways from) to genital ridge

Question 23

Outline what happens to Mesonephric cells in females

Answer 23

In females = No SRY expression

They form vascular tissue
Theca cells

Question 24

Outline what happens to Mesonephric cells in males

Answer 24

In Males= SRY expression

They form:
Vascular tissue
Leydig cells (testosterone)
Basement membrane (forms the seminiferous tubules and rete-testis

Question 25

What are the two types of internal reproductive organs ?

Answer 25

Mullerian ducts (Female )
Inhibited through AMH in men

Wolffian ducts
Stimulated by testosterone
Lack of stimulation through testosterone makes it regress in females

Question 26

Outline the structure of the male internal sexual differentiation

Answer 26

Gonad
Mesonephros 
Mullerian duct,
Wollfian duct
Cloaca 

IN MALE BECOME :

Epididymis 
Testis
Vas deferens
Urinary bladder
Seminal vesicle 
Prostate gland

Question 27

What is the Cloaca ?

Answer 27

Early in the development of a female foetus, the tissue that is supposed to become the intestinal, genital, and urinary tracts are together in one unit known as a “cloaca.” These three typically separate as a pregnancy proceeds, creating the anus, the vagina, and the urethra

Question 28

Outline the structure of the female internal sexual differentiation ?

Answer 28

Ovary 
Oviduct
Degenerating Wolffian duct
Uterus 
Urinary bladder 
Vagina

Question 29

What does testosterone get converted into during external differentiation and where does this take place?

Answer 29

The more potent androgen DHT(dihydrotestosterone) via 5-a-reductase in the genital skin.

Question 30

What does DHT do ?

Answer 30

DHT causes differentiation of the male external genitalia :

Clitoral area will enlarge into the penis
Labia will fuse and become ruggated to form the scrotum
The prostate will form

Question 31

What are the two factors at play during nature or nurture ?

Answer 31

Psychosexual neutrality:
The view that gender assignment of a new-born with ambiguous genitalia can be made regardless of the endocrine history

Neutral bias:
The idea that a tendency for male or female is already present in neonates as a result of prenatal factors such as the hormonal milieu (background) in utero