1- Sexual Determination And Disorders Flashcards
What is sexual determination?
Genetically controlled process dependent on the switch on the Y chromosome
Chromosomal determination of male and female
Male- XY
Female- XX
What is sexual differentiation?
The process by which internal an external genitalia develop as male and female
How is gonadal sex determined?
Sex determining region Y (SRY)switches on after week 7 of embryo development
gonad turns into testis
testis develop and produce AMH and testosterone
What is the precursor for gonadal development?
The gonadal ridge
What are the 3 waves of cells that invade the genital ridge?
Primodal Germ cells - sperm/ oocytes
Primitive sex cords - Sertoli cells (male)/ granulosa cells (female)
Mesonephric Cells - blood vessels and Leydig cells (male) / theca cells (female)
What is the process of sexual differentiation?
genotypic sex ( xy/xx)
gonadal sex (ovaries/testis)
phenotypic sex (genitalia)
legal sex
gender identity
What are the two ducts present in the embryo before sex determination
Mullerian duct - female
Wolffain duct - male
What does the term bipotential mean in relation to the gonads?
They are able to differentiate into either testis or ovaries
Describe primordial germ cell migration
An initially small cluster of cells in the epithelium of the yolk sac expands by mitosis at around 3 weeks
They then migrate to the connective tissue of the hind gut, to the region of the developing kidney and in to the genital ridge
This process is completed by 6 weeks
Describe the formation of the sex cords
Cells from the germinal epithelium that overlies the genital ridge mesenchyme migrate inwards as columns called the primitive sex cords
Male-
- there’s SRY expression
- penetrate medullary mesenchyme & surround primordial germ cells to form testis cords – precursor of seminiferous tubules.
- eventually become Sertoli cells that express AMH.
Female-
- there’s no SRY expression
- sex cords ill defined and do not penetrate deeply but instead condense in the cortex as small clusters around primordial germ cells – precursor of ovarian follicle
- eventually become granulosa cells
Describe the role of mesospheric cells in gonadal development
These originate in the mesonephric primordium which are just lateral to the genital ridges
In males they act under the influence of pre-Sertoli cells (which themselves express SRY) to form…
- Vascular tissue
- Leydig cells (synthesize testosterone, do not express SRY)
- Basement membrane – contributing to formation of seminiferous tubules and rete-testis
In females without the influence of SRY they form…
- Vascular tissue
- Theca cells
What do primordial cells become in males and in females?
Males: spermatozoa
Females: oocytes
What do the primitive sex cords become in males and in females?
Males: Sertoli cells (express SRY and produce AMH)
Females: Granulosa cells
What do mesonpheric cells become in males and in females?
Males: Leydig cells (produce androgens- testosterone)
Females: Theca cells
What are the 2 main internal ducts that develop into internal reproductive organs?
Mullerian ducts:
- most important in females
- inhibited in the male by AMH
Wolffian ducts:
- most important in males
- stimulated by testosterone
- lack of stimulation by testosterone means regression females
How does internal sexual differentiation occur?
Males:
- AMH secreted by Sertoli cells regresses the Mullerian duct
- testosterone secreted by the Leydig cells grows the wolffian duct
Females:
- no AMH so Mullerian duct grows
- no testosterone so wolffian duct regresses
- Mullerian duct develops into uterine tubes, uterus and part of the vagina
What is function of 5-alpha reductase in external differentiation?
It converts testosterone in the genital skin to the more potent DHT (dihydrotestosterone)
What is the function of DHT?
DHT binds to the testosterone receptor, but is more potent that testosterone
DHT causes differentiation of the male external genitalia:
- Clitoral area enlarges into penis
- Labia fuse and become ruggated to form scrotum
- Prostate forms
What is the function of 5- alpha reductase in females?
5- alpha reductase is present but there is no testosterone to be converted to DHT
Therefore no differentiation of external genitalia into male genitals
What are the different types of sexual differentiation disorders?
Gonadal dysgenesis:
- Sexual differentiation is incomplete.
- Usually missing SRY in male, or partial or complete deletion of second X in female.
- Also used as a general description of abnormal development of the gonads.
Sex Reversal:
- Phenotype does not match genotype, ie may be male genotypically but externally look like a female.
Intersex:
- Have some components of both tracts or have ambiguous genitalia. Sex of infant difficult to determine.
What happens when an XY individual has testosterone but it has no effect?
- gonadal dysgenesis disorder
- it is known as androgen insensitivity syndrome (AIS)
What happens in individuals of AIS?
- AIS: androgen insensitivity syndrome
- Testes form and make AMH so Mullerian ducts regress.
- No differentiation of Wolffian ducts
- No external male genitalia
What are the differences between partial and complete AIS?
Complete AIS:
- Appear completely female at birth and assigned female gender despite being XY.
- Have undescended testes.
Diagnosis:
- Usually present with primary amenorrhoea. Lack of body hair is a clue.
- Ultrasound scan and karyotype with male levels of androgens.
- Never responded to androgen so appear and often feel female.
Partial AIS:
- Present with varying degrees of penile and scrotal development from ambiguous genitalia to large clitoris.
- Surgery was universal but now fortunately considered optional or at least best delayed. Decisions made on potential. Very difficult for parents.
What happens if an XY individual testosterone is made but its not converted into DHT?
- gonadal dysgenesis
- 5- alpha reductase deficiency syndrome
What happens?
- Testes form and make AMH so Mullerian ducts regress.
- Wolffian ducts develop
- No external male genitals
