Normal Sexual Differentiation Flashcards
Define sexual determination
Genetically controlled process which is dependant on the switch on the Y chromosome.
Determines male /female on chromosomal level
Define Sexual differentiation
This is the process by which internal and external genitalia will develop as male or female
What gene determines the development of male gonads?
The SRY gene
What does the presence of the SRY gene determine ?
The SRY gene will lead to testis determination.
This is switched on briefly during embryo development and makes gonad into testis.
What will happen when there is no SRY gene ?
This will cause the development of ovaries
Define gonadal sex
This is defined as the sex as determined on the basis of the gonadal tissue present
(Ovary vs Testis )
What are the hormones made in the Testis and what cells secrete them ?
Sertoli cells - AMH (Anti-Mullerian hormone )
Leydig cells - Testosterone
What is Euchromatin ?
This is lightly packed form which is enriched
How does the SRY gene act as a transcription factor ?
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.
What is heterochromatin ?
This is tightly packed form of DNA which is condensed and inactive for transcription.
What is the affect of the AMH hormone ?
This stops the development of the Mullerian duct in males
What is the critical site of DNA binding involved with the SRY gene ?
This is found upstream to the SOX9 gene which is also a transcription factor
Outline the mechanism of the SOX9
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
How does SOX9 work?
SOX9 works by keeping ovarian genes off , swithcing on testicular genes and keeping these on.
This causes the development of male gonads/genitalia
How does SOX9 achieve its effects ?
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 )
What would the Mullerian duct develop into in the absence of AMH ?
The fallopian tube and the uterus
internal female genitalia
Describe the early stage of gonad development
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
Outline the development process of the genital ridge
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
What is the process of primordial germ cell migration?
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 )
What is the process primitive sex cord migration in female ?
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
What is the process of primitive sex cord migration in males?
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 .
Define Mesonephric cells and where they come from
These originate in the mesonephric primordium which is found lateral (sideways from) to genital ridge
Outline what happens to Mesonephric cells in females
In females = No SRY expression
They form vascular tissue
Theca cells
Outline what happens to Mesonephric cells in males
In Males= SRY expression
They form:
Vascular tissue
Leydig cells (testosterone)
Basement membrane (forms the seminiferous tubules and rete-testis
What are the two types of internal reproductive organs ?
Mullerian ducts (Female ) Inhibited through AMH in men
Wolffian ducts
Stimulated by testosterone
Lack of stimulation through testosterone makes it regress in females
Outline the structure of the male internal sexual differentiation
Gonad Mesonephros Mullerian duct, Wollfian duct Cloaca
IN MALE BECOME :
Epididymis Testis Vas deferens Urinary bladder Seminal vesicle Prostate gland
What is the Cloaca ?
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
Outline the structure of the female internal sexual differentiation ?
Ovary Oviduct Degenerating Wolffian duct Uterus Urinary bladder Vagina
What does testosterone get converted into during external differentiation and where does this take place?
The more potent androgen DHT(dihydrotestosterone) via 5-a-reductase in the genital skin.
What does DHT do ?
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
What are the two factors at play during nature or nurture ?
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
