Sexual Differentiation Flashcards
What are the 3 levels of Sexual Differentiation
- Gonads
- Internal Genitalia
- External Genitalia
What is meant by the ‘bipotential gonads’
That we all have the potential to be male or female! Irrespective of your chromosomes.
Bipotential Gonads <6wks
Bipotential Internal genitalia <7wks
Bipotential Eternal Genitalia <8wks
What determines internal and external sexual differentiation?
The Testis. Dominant > male
An ovary or NO gonad will result in female internal and external genitalia.
Describe the origin of the bipotential gonad/genital ridge
- Arise as paired structures in intermediate mesoderm
- Genital ridge area can be divided into 3 (from ant- post)
- Pronephros (caudal end forms adrenals)
- Mesonephros (central region forms the gonads and internal reproductive structures; wolffian + mullerian ducts
- Metanephros (post end forms kidneys)
- Therefore if you’ve got a defct in your gonads, you could have a defect in your adrenals or your kidneys, look at these structures as a signal of this
Describe the origin of the bipotential gonad/genital ridge
- The development of the GR is dependent on the activation of nuclear transcription factors
- These proteins bind and form part of the protein complex around DNA altering gene transcription/expression
- Because adrenal, gonadal and renal organogenesis occurs from the GR, their development occurs from similar transcription factors.
Mutations in these affect more then one organ system
4 main genes involved in gonadal development?
- IGFR1 insulin like growth factor receptor 1
- Wilms Tumour 1 (WT1) kidney tumour you get in kids
- Steroidigenic Factor 1 (SF1) found in lots of tissues
- DAX1
These are all important in getting mesoderm → genital ridge.
From genital ridge you get your ovaries and testis forming
At the same time as the int. mesoderm is forming the GR, _____ cells from the _________.
At the same time as the int. mesoderm is forming the GR, germ cells from the yolk sac endoderm.
They migrate up a conc gradient to Stem Cell Factor, via C-kit receptors, has a role in ovarian development.
What will loss of function in a gene that is critical to forming the gonadal ridge cause?
No gonads formed ⇒ female internal and external genitalia
What initiates gonadal determination to either a testis or ovarys?
- Testicular determination* → initiated in most mammals by SRY (sex determining region of Y)
- Ovarian Initiator* → unknown (maybe FOXL2)
- Multiple genes are involved in each process
- earlier + greater gene activation in testicular development
- More is know about testis formation
Describe and draw out this image (MEMORISE)
Ovaries: Driven by FOXL2. Also by Bcatenin**, RSPO1, DAX-1, WnT4
♦ As well as driving ovarian development it inhibits testicular formation
Testis: Driven by SRY (only present for first 24hrs), who’s main job is to activate SOX-9. Also SF-1 and FGF9
♦♦As well as driving Testicular development it inhibits ovarian formation
SRY of the male gonadal determination
SRY is the sex determining region of Y, and is the initial gene determining male gonadal development.
Identified in 1991 from XXmales (chromosome been transfered Y→X during recombination)
FOund solely in the pre-Sertoli cell in the testis and activation precedes development of the Sertoli cell (which is already the 1st of testicular cells)
Sertoli Cells: testis ‘regulator cell’ and blood-testis barrier (prevents WBC interacting with sperm and provides nutrients)
SRY’s main role is?
To stimulate SOX-9
SOX-9: autosomal gene that once stimulate`d completes testicular differentiation
Initial SOX-9 transcription from SF-1
Then hugely upregulated by SRY
Finally upregulates itself via a positive feedback loop and the stimulation of prostaglandin D2 and FGF-9
These ALL inhibit ovarian Transcription Factors also
Prostaglandin D2 role and origin?
Produced from pre-sertoli cells.
Increases SOX-9 in a paracrine manner, (binds to PG receptors on cells)
Recruits further undifferentiated cells → sertoli cell lineage
A cascade effect.
FGF-9
FGF-9 is a crucial growth factor for male sex determination, also acts as the earliest mitogen in the XY gonad.
Secreted from pre-Sertoli cells, enhances proliferation of SF-1 positive cells of coelomic epithelium → increased number of precursors of Sry-expressing cells and other gonadal cells
Therefore involves in both sex determination and testis differentiation
Leydig cell equivalent to ______
Sertoli Cells equivalent to _____
What do Leydig cells do?
Leydig cell equivalent to Thecal cell
Sertoli Cells equivalent to Follicular cell
They are your ‘steroid factory’ (steroidogenic function of testis), and arise from within the interstitium of the testis, outside the cords.
Initial fetal Leydig cells regress and are replaced by adult Leydig cells post natally.
They make Testosterone!! (sertoli make everything else)
