Reproduction: Sexual Differentiation & Disorders Flashcards
What is sexual determination?
Genetically controlled process dependent on the ‘switch’ on the Y chromosome which determines whether someone will be a male or female.
What is sexual differentiation?
The process by which internal and external genitalia develop as male or female
What are the different types of sex?
- Genotypic sex - Whether a person’s genome contains two X chromosomes (female) or an X and a Y chromosome (Male)
- Gonadal sex - Whether a person’s gonads become testes or ovaries
- Phenotypic sex - Development of particular external genitalia e.g. Vulva or penis
- Legal sex - Sex that is on a persons birth certificate
- Gender identity - What gender a person identifies as
What gene present on the Y chromosome is responsible for determining gonadal sex?
SRY gene
Briefly describe how the SRY gene determines gonadal sex
- SRY gene switches on briefly during embryo development which causes it to induce its own transcription to produce the SRY protein
- SRY protein then causes the production of lots of other proteins that results in the gonad differentitating into the testis
If there’s no SRY gene present what do the gonads differentiate into?
Ovaries
Why are gonads said to have bipotential?
Because they have the ability to develop into either male or female internal genitalia and the chances of them developing into either one are equal
What is the name of the structure that is a precursor to the gonads?
Genital ridge
Where do the genital ridges develop within an embryo and after how many weeks do they develop?
- They develop at the posterior wall of lower thoracic lumbar region.
- They develop after 3½ - 4½ weeks
There are 3 cell types that will invade the genital ridges during their development, what are the names of these 3 cell types?
- Primordial germ cells
- Primitive sex cords
- Mesonephric cells
Each of the cell types that invade the genital ridges also have bipotential. Give the names of the cells that each of these cell types can differentiate into
- Primoridial germ cells: Differentiate into Sperm (male) or Oocyte (female)
- Primitive sex cords: Differentiate into Sertoli cells (male) or Granulosa cells (female)
- Mesonephric cells: Differentiate into Blood vessels and Leydig cells (male) or Theca cells (female)
Where to the primordial germ cells initially develop and by what process do they develop?
- Primordial germ cells start off as small cluster of cells in the epithelium of the yolk sac of the embryo
- They begin to develop/expand via mitosis
What pathway do the primordial germ cells take to migrate to the genital ridges?
They migrate from the yolk sac, through the connective tissue of the hind gut, to the region of the developing kidney and on to the genital ridge
Once the primordial germ cells have migrated to the genital ridges what occurs to the primitive sex cords?
The primitive sex cords migrate from epithelium that overlies the genital ridge to the genital ridge itself and associates with the primordial germ cells already present
Describe what happens to the primitive sex cords specifically in males
- In males the primitive sex cords penetrate deeply into the genital ridges and completely surrond the primordial germ cells to form a tube-like structure
- In males the primitive sex cords do have the SRY gene and so they express it
- This eventually causes the primitive sex cords to differentiate into Sertoli cells
In males, what causes the primordial germ cells to differentiate into Spermatozoa?
- When the Sertoli cells that differentiated from the primitive sex cords that surronded the primoridal germ cells come into contact with one another
- Primordial germ cells get exposed to the expressed SRY from the Sertoli cells which is specifically what causes them to differentiate
What hormone do the Sertoli cells secrete?
They secrete the Anti-mullerian hormone (AMH)
Describe what happens to the primitive sex cords specifically in females
- In females the primitive sex cords don’t penetrate that deeply into the genital ridges and instead of completely surronding the primordial germ cells they form small clusters around them
- In females the primordial germ cells don’t express the SRY gene and so they differentiate into Granulosa cells
In females, what causes the primordial germ cells to differentiate Oocytes?
- When the Granulosa cells that differentiated from the primitive sex cords that surronded the primordial germ cells in clusters come into contact
- Granulosa cells don’t express SRY so without this primordial germ cells differentiate into Oocytes
Once the primitive sex cords reach the genital ridges in males, what happens to the mesonephric cells?
- They migrate from the mesonephric primordium, which is just lateral to the genital ridges, to the genital ridges.
- Then under the influence of the SRY produced by the developing Sertoli cells the mesonephric cells differentiate to form:
- Vascular tissue
- Leydig cells (mainly differentitate into these)
- Basement membrane – Later contributes to formation of seminiferous tubules
What hormone do the Leydig cells secrete?
Testosterone
Once the primitive sex cords reach the genital ridges in females, what happens to the mesonephric cells?
- They also migrate from mesonephric primordium to the genital ridges and because they aren’t under the influence of SRY they differentiate to form:
- Vascular tissue
- Theca cells
Explain how the internal sexual organs develop in males
- Before internal sex organ development males contain both the Mullerian and Wolffian ducts
- The developing testis contain both Sertoli and Leydig cells
- The sertoli cells secrete Anti-Mullerian hormone which will result in the regression of the Mullerian duct
- The leydig cells secrete Testosterone which causes the growth of the Wolffian duct which will develop into the Epididymis, Vas deferens and the Seminal vesicle.
Explain how the internal sexual organs develop in females
- Before sexual organ development females also contain both Mullerian and Wolffian ducts
- Because the developing ovaries don’t secrete Anti-Mullerian hormone it means the Mullerian duct is able to grow and develop into the uterus, uterine tubes and upper 1/3rd of the vagina
- Because the developing ovaries also don’t secrete Testosterone it means that the Wolffian duct regresses
In males what changes occur during the development of the external genitalia?
- Genital tubercule forms the glans penis (head of penis)
- Genital swellings fold in themselves to form the scrotum
- Scrotal skin becomes ruggated
- Prostate forms
What substrate induces the development of the male external genitalia and how is this substrate produced?
- Dihydrotestosterone induces development of male external genitalia
- Produced via reaction that converts testerone into dihydrotestosterone
- Reaction catalysed by 5-α-reductase found in genital skin
In females what changes occur during the development of the external genitalia?
- Genital tubercule develops into clitoris
- Urethral fold becomes opening to the vagina and the Labia minora
- Genital swelling becomes Labia majora
What are some disorders of sexual differentiation?
- Gonadal dysgenesis - Disorder in which sexual differentiation is incomplete
- Sexual reversal - Disorder in which a person’s phenotype does not match their genotype
- Intersex - Disorder in which a person has some components of both genitalia
Gonadal dysgenesis can occur due to Androgen insensitivity syndrome, what is androgen insensitivity syndrome?
Androgen insensitivity syndrome is when a person who is genetically male (XY) is resistant to androgens (male hormones) such as testosterone
What changes in sexual differentiation occur due to Androgen insensitivity syndrome?
- Testosterone doesn’t have any effect so the Wolffian duct isn’t able to grow.
- This means it isn;t able to develop into the vas deferens, Epididymis etc.
- Anti-Mullerian hormone is still produced so the Mullerian duct regresses - this means no internal genitalia develop
- Testosterone still coverted into dihydrotestosterone but this won’t have an effect because testosterone receptors are faulty
- This means female external genitalia will develop instead
What are the 2 different types of Androgen insensitivity syndrome?
- Complete androgen insensitivity syndrome - Appear completely female at birth and assigned female gender despite being XY.
- Incomplete androgen insensitivity syndrome - Present with varying degrees of male/female external genitalia
Gonadal dysgeneis can also be caused by 5-α-reductase deficiency. What changes in sexual differentiation occur due to 5-α-reductase deficiency?
- 5-α-reductase deficiency means testosterone isn’t converted into dihydrotestosterone
- Without dihydrotestosterone male external genitalia development isn’t able to be induced
- This means female external genitalia will develop
- Male internal genitalia will develop as normal
Why does the incidence of 5-α-reductase deficiency vary?
Varies because it’s autosomal recessive which means a person can be a carrier or have 2 copies of a variant that causes 5-α-reductase deficiency
Gonadal dysgenesis can also be caused by turner syndrome. What is turner syndrome?
Syndrome that results in a person only having one X chromosome rather than having two X’s and an X and a Y.
What changes in sexual differentiation will occur as a result of turner’s syndrome?
- Person only has one X so genetic sex is female
- Female internal and external differentiation will occur as normal
If Turner’s syndrome doesn’t cause a problem with female genitalia development then what problems do occur?
- Failure of ovarian function
- Uterus and uterine tubes are present but small, other defects in growth and development.
If females only ever express one X chromosome in all their cells why do females with Turner syndrome exhibit symptoms?
- It’s beleived that not every single gene on the other X chromosome is inactivated due to X-inactivation
- Also believed that these genes are important for particular functions
Gonadal dysgenesis can also be caused by Congenital adrenal hyperplasia. What is Congenital adrenal hyperplasia?
- A group of disorders which reuslts in a deficiency of one of the enzymes needed to cause the adrenal glands to secrete cortisol
21-Hyrooxylase is one of the enzymes that can be affected by Congenital adrenal hyperplasia. What reaction does 21-Hyrooxylase catalyse?
Catalyses the conversion of Progestagens, e.g. progesterone into Glucocorticoids, e.g. Cortisol, and Mineralocorticoids
21-Hyrooxylase deficiency can lead to failure to synthesise cortisol. What effects can this cause?
- No cortisol leads to production of Corticotropin releasing hormone (CRH) and Adrenocorticotropic hormone (ACTH) by hypothalamus and pituitary gland
- ACTH causes cholesterol uptake into the adrenal glands
- In the adrenal glands cholesterol is converted into progestagens which would normally be converted into aldosterone and cortisol
- However, due to 21-Hyrooxylase deficiency the cholesterol can’t be converted into cortisol s it leads to a build up of aldosterone.
What changes to sexual differentiation are caused by Congenital adrenal hyperplasia?
- Results in a female being exposed to high levels of androgens, e.g. testosterone
- Still growth in Mullerian ducts due to no anti-mullerian hormone as they’re aren’t any Sertoli cells - Females have ovaries not testis
- This means you get development of female internal genitalia
- Incomplete Wolffian duct regression due to presecence of testosterone
- Male extrnal genitalia development due to prescence of testosterone (gest converted into dihydrotestosterone).
