Sex Determination Flashcards
What is sex determination?
Progress of development of sex differences. Defined as the phenotypic development of structures consequent upon the action of hormones produced following gonadal determination.
What did we think historically about sex determination?
They believed that the warmer it was when conception happened the more likely you would be to get a boy and if you got a girl it was because the women’s coldness over took the mans heat and mutilated their son into a girl.
How is sex actually determined?
Chromosomes
What chromosomes do males have?
XY
What chromosomes do females have?
XX
Who in a partership determines sex?
Male - its the sperm thats giving the x or the y not the egg
Do all organ rudiments differentiate into only one type of organ?
No, the only one that does not is the gonadal rudiment which can become either testes or ovaries.
What is the indifferent stage?
The fetus has the chromosomes that will become male or female but they are at the bipotential stage - nothing has differentiated yet
All embryos are default what?
Females
What week is ‘decision time’ for am embryo?
Week 7
During the bipotential stage (before week 7) would you be able to tell what gender the baby would be?
No
What are the germ cells in the gonads?
Oocyte and sperm
What are the somatic cells in the gonads?
Granulosa (supports oocyte) and sertoli cells (support sperm)
What are the steroidogenic cells in the gonads?
Theca (Oestrogen) and leydig (testosterone)
What are the cells that we start off with in life (that will become either sperm or oocytes)?
Primordial germ cells
When does specification of PGC’s begin?
Week 3 of human gestation
Where are PGC’s originally seen?
In the yolk sac
Where do germ cells form then is PGC’s develop in the yolk sac?
In the yolk sac which is outside of the body
Where does the gonads move too from the yolk sac?
The gonadal/genital ridge which is on the medial side of the mesonepthros (fetal interim kidney)
What is the PGC migration pathway?
From yolk sac through the hindgut and the dorsal mesentery (fold of tissue that attaches organs to body wall) and to the genital ridges
What are PGCs doing whilst they migrate?
Proliferate
What does PGC motility require?
1) Chemotactic signals
2) Gradient of extracellular matrix glycoproteins
3) PGC-PGC contact
Do PGC’s need to divide into two populations?
Yes to go into the left and right gonads
What signals are needed for PGC migration?
- TGF beta
- Kit ligand/ stem cell factor
- bFGF
Are germ cells sexually bipotential during migration?
Yes
When does sex specific differentiation of PGCs begin?
After they have colonised the gonad as it depends on what somatic cells are found there either granulosa or leydig cells
What happens to the PGC’s at the gonad?
They are surrounded by somatic cells and continue to proliferate. At this point they differentiate into either Prespermatogonia/prospermatogonia (males) or oogonia (females)
What genes regulate gonadal development?
Steriodogenic factor 1 gene
What is primary sex determination?
The indifferent gonad becoming either an ovary or a testis
What is secondary sex differation?
The testis and ovaries making sex characteristics
How did we know what the testis/ ovaries did (Jost Paradigm)?
Jost removed ovaries and testis from rabbits in utero and put the rabbit back. He found that females without ovaries still made a female genotype and males with testis removed made the male phenotype.
What hormones cause sexual dimorphisms?
Testosterone and antimullerian hormone
What would happen if you gave a female testosterone in fetal development?
It showed male phenotypes
What is the default process?
Female development
How does the indifferent gonad make males then?
There must be a maleness factor triggering development of the testes. The testes then secrete testosterone and AMH which causes male secondary sexual differentiation
What are the structures of the indifferent gonad?
Bipotential gonad
Mullerian duct
Wollferian duct
What will mullerian ducts go on to become?
Uterus, oviduct, cervix, upper vagina
What receptors do mullerian ducts have?
AMH
In order to survive do mullerian duct receptors need to see or not see AMH?
Not see (remember this is secreted from testes)
What happens to the wollfian duct in female development?
Is disengages (disappears)
In males what stays - mullerian or wolffian duct?
Wolffian duct
What does the wolffian duct develop into?
Vas deferens
Epididymus
Seminal Vesicles
What receptors do wolffian ducts have?
Androgens
What do the wolffian ducts need for survival?
Testosterone (this is why they disappear in females as there is no testosterone).
In males what happens to the mullerian duct?
They regress due to AMH being secreted from the testis
What do the mesenchume cells of the ovary become?
Theca cells
What cells produce AMH?
Sertoli cells
What cells produce testosterone?
Leydig cells
What is the maleness factor found in the chromosomes which trigger differentiation into testes?
SRY gene found on the Y chromosome
What does the SRY gene do?
Has DNA binding properties which encodes a transcription factor and is the genetic switch (switching genes on the X chromosome on)
Where is the SRY gene expressed?
Somatic cells and sertoli cells
What genes are expressed when SRY is on?
Sox9 which induces testis formation and if this is found in someone with XX chromosomes they will still be male
SF-1 which is a transcription factor that activates several genes involved in steroid synthesis
What two genes lead to the production of AMH?
SF-1 and Sox9
Is there a long or short window you can affect the SRY gene?
Short
Are you continously supressing male/female development throughout life?
Yes
Is there a specific gene which makes ovaries?
No - there is many genes which affect the amount and patterns of proteins
What is DAX1?
Nuclear hormone receptor involved in many hormone production including ovary and testis
Can you be XY and still have female genotypes?
Yes if you have a duplication of the X chromosome
What does Wnt4 do?
Activates beta catenin signalling and is expressed in the indifferent gonad. It is undetectable in the testes but maintained in the ovaries
What happens in XY individuals with duplication of the Wnt4 gene?
They overproduce DAX1 and ovaries form
What could drive ovary development?
Wnt4 and DAX1
What are the 3 different types of differences of sex development?
Sex Chromosome DSDs
46 XX DSDs
46 XY DSDs
What causes sex chromosome DSDs?
abnormalilites in the sex chromosomes e.g. turners, Klinfelter
What causes 46 XX DSDs?
androgen excess during pregnancy e.g. congenital adrenal hyperplasia
What causes 46 XY DSDs?
incomplete intrauterine masculinization caused by abnormal testis development or defects in androgens e.g. 5 alpha reductase type 2 deficiency (people begin as female but during puberty become male).
DSDs are cuased by what?
Aneuploidy which is either monosomy and trisomy
What causes turner sydrome?
1 X chromosome and results in absent ovaries, short stature etc.
How do birds determine sex?
Females have a ZW chromosome
Males have ZZ chromosomes
How do flies do sex determination?
Females = the y chromosome does nothing
Males = its the ratio of the X chromosomes leads to autosomes determining the sexual phenotype
How do ants and wasps form?
Females from fertilized diploid eggs
Males from unfertilized haploid eggs
What is environmental sex regulation?
When the temperature of the egg at specific points determines the sex of animals such as crocodiles and turtles after fertilisation.
How does temperature regulate sex?
All thermosensitive animals go through a thermosensitive period between 28 - 52 days and it is after this point they start developing sex characteristics before this they have an indifferent gonad.
Thermosensitivity - what are the genes behind this sex determination?
The expression of the Sox9 gene changes in response to temperature (higher temp = lower Sox9, lower temp = higher Sox9).
What are clown fish?
Hermaphrodites - they start of their life as one sex and switch to another
How do clown fish change gender?
There is one sexually mature breeding pair per group (male and female) and all other fish are males.
If the female dies her male mate becomes female and the next largest male takes their place as the new sexually mature mate.
