REPRO: Sexual Differentiation and Disorders Flashcards
What is sexual determination?
It is a genetically controlled process dependant on the ‘switch’ on the Y chromosome. Chromosomal determination tells you if you’re male or female.
What is sexual differentiation?
It is the process by which internal and external genitalia develop as male or female.
What are the different levels of sexual differentiation, from embryo to adult?
- genotypic sex (if the embryo has XX or XY)
- gonadal sex (either ovaries or testes develop)
- phenotypic sex (outward appearance)
- legal sex (what’s written on the passport)
- gender identity (how you feel)
Describe how the SRY gene is involved in gonadal development.
The SRY gene is a transcription factor that transcribes itself (positive feedback), along with a transcriptional cascade of events that eventually leads to the development of a testis. In the absence of this gene, ovaries develop.
SRY is the triggering event for sexual differentiation.
The testis develops cells that make 2 important hormones:
- SERTOLI cells produce anti-Mullerian hormone (AMH)
- LEYDIG cells make testosterone
Products of the testis influence further gonadal and phenotypic sexual development.
Describe gonadal development after fertilisation.
After fertilisation, a pair of gonads develops which are bipotential.
Their precursor is derived from common somatic mesenchymal tissue precursors called the genital ridge primordia (3.5 to 4.5 weeks) on the posterior wall of the lower thoracic lumbar region.
What are the three waves of cells that invade the genital ridge?
- Primordial Germ Cells - become sperm (male) or oocytes (female)
- Primitive Sex Cords - become Sertoli cells (male) or Granulosa cells (female)
- Mesonephric Cells - become blood vessels and Leydig cells (male) or Theca cells (female)
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 hindgut, to the region of the developing kidney and on to the genital ridge - completed by 6 weeks.
These cells can become either oocytes or sperm
Describe the formation of the sex cords (Sertoli/Granulosa).
Cells from the germinal epithelium that overlies the genital ridge mesenchyme migrate inwards as columns called the primitive sex cords.
In MALES:
- There is SRY expression
- The sex chords penetrate the medullary mesenchyme and surround the PGCs to form the testis chords.
- They eventually become Sertoli cells, which express anti-Mullerian hormone (AMH).
In FEMALES:
- There is no SRY expression.
- The sex chords are ill-defined and do not penetrate deeply, but instead condense in the cortex as small clusters around PGCs.
- They eventually become Granulosa cells.
Describe the role of mesonephric cells in gonadal development.
These originate in the mesonephric primordium, which is just lateral to the genital ridges.
In MALES, they act under the influence of pre-Sertoli cells to form:
- vascular tissue
- Leydig cells (synthesise testosterone, don’t express SRY)
- basement membrane - contributing to the formation of seminiferous tubules and rete-testis
In FEMALES, they form:
- vascular tissue
- Theca cells (synthesise androstenedione, which is a substrate for estradiol production by the granulosa)
What are the two main structures involved in developing internal reproductive organs?
Mullerian ducts:
- most important in female
- inhibited in males by AMH
Wolffian ducts:
- most important in the male, stimulated by testosterone
- lack of stimulation by testosterone means regression in female
Describe the role of 5-α-reductase in external differentiation.
Testosterone is converted to the more potent androgen DHT (dihydrotestosterone) by 5-α-reductase in the genital skin.
DHT also binds to the testosterone receptor but is more potent than testosterone.
DHT causes differentiation of the male external genitalia:
- clitoral area enlarges into the penis
- labia fuse and become ruggated to form the scrotum
- the prostate forms
It is present in both males and females, but because there is no substrate (testosterone) in females, its effects don’t play out.
List some disorders of sexual differentiation.
- gonadal dysgenesis: sexual differentiation is incomplete; also used as a general description of the abnormal development of the gonads
- sex reversal: phenotype not matching the genotype
- intersex: have some components of both tracts, or have ambiguous genitalia
What is it called when testosterone is being made in an XY individual, but it has no effect?
What does that result in?
Androgen Insensitivity Syndrome (AIS).
The testes form and make AMH so the Mullarian ducts regress. There is no differentiation of the Wolffian ducts, and thus no external male genitalia.
What’s the difference between complete and partial AIS?
Complete AIS:
- appear completely female at birth, and are assigned the female gender despite being XY
- usually present with primary amenorrhoea, lack of body hair is a clue
- would be diagnosed by ultrasound scan and karyotype with male levels of androgens
- would never respond to androgen so they appear and 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 (at least best, delayed)
- decisions made on potential, very difficult for parents
What is it called when testosterone is made in an XY individual, but not DHT?
What does that result in?
5-α-reductase Deficiency.
The testes form and make AMH so the Mullerian ducts regress. The Wolffian ducts then develop, but there is no external male genitalia.
