Lecture 1 Flashcards
What is sexual determination?
Genetically controlled process dependent on ‘switch’ on Y chromosome
Chromosomal determination of male or female.
What is sexual differentiation?
Process by which internal and external genitalia develop as male or female
Describe the relationship between sexual determination and differentiation
The two processes are contiguous and consist of several stages
Which gene is responsible for testicular formation?
SRY gene
What is the SRY gene?
Gene found on the short arm of the Y chromosome that creates the testes.
What happens in the absence of the Y chromosome?
Development of ovaries
When does the SRY gene produce its effects?
Switches on briefly during embryo development (>week 7) to make gonad into a testis
Name the testicular cells and their hormone secretions
Sertoli cells: AMH
Leydig cells: Testosterone
What are the effects of testicular hormone release?
Products of testis influence further gonadal and phenotypic sexual development
Describe the structure and function of SRY gene
SRY is a DNA binding protein that acts as a transcription factor
What transcription factors are responsible for testis formation?
SRY and SOX9 are TF that turn OFF genes promoting ovarian development, leading to testicular formation
Where does DNA bind during testis formation?
Critical site of DNA binding is upstream of SOX9
How is SOX9 activated?
SOX9 can bind own upstream activation site = levels remain high even if SRY declines.
+ve feedback mechanism.
What are the effects of SOX9 activation?
SOX9 acts to stimulate expression of further downstream genes ==> become Sertoli cell
Describe the relationship between SRY and SOX9
SRY determines executive policy and SOX9 implements it
What are the 4 mechanisms of SOX9 action?
- PDG2 production
- FGF9 production
- AMH production
- Female TF WNT4 / FOXL2 inhibition
How does SOX9 stimulate PDG2 secretion?
Via pre-sertoli cells
What is the effect of SOX9 PGD2 secretion?
PGD2 acts as a paracrine hormone to stimulate further SOX9 production in pre-sertoli cells
2nd +ve feedback ensures all precursor cells commit to sertoli cell pathway
What are the effects of SOX9 FGF9 production?
Acts as a chemotactic factor for cell migration into developing testis.
Further stimulates SOX9 production
3rd +ve feedback mechanism
Describe the effects of SOX9 AMH production
Causes regression of mullerian ducts which develop into uterus and fallopian tubes in females
What occurs in the absence of SRY gene?
WNT4 and FOXL2 are stimulated.
FOXL2 inhibits SOX9
What happens after fertilisation in gonadal development?
A pair of bipotential gonads develop.