Normal sexual differentiation Flashcards
Describe the differences between sex determination and differentiation
Sexual determination: Genetically controlled process dependent on the ‘switch’ on the Y chromosome. Chromosomal determination of male or female
Sexual differentiation: The process by which internal and external genitalia develop as male or female.
The two processes are contiguous and consist of several stages.
what gene determines gonadal sex
SRY gene creates the testis.
In the absence of Y chromosome ovaries develop.
Sex determining region Y (SRY) switches on briefly during embryo development (>week 7) to make the gonad into a testis. In its absence an ovary is formed.
What cells do the testis make
Testis develops cells that make 2 important hormones:
Sertoli cells produce anti-Mullerian hormone (AMH).
Leydig cells make testosterone.
Products of testis influence further gonadal and phenotypic sexual development.
Describe the mechanism of SRY action
SRY is a DNA-binding protein that acts as a transcription factor.
The critical site of DNA binding is upstream of SOX9 which is also a transcription factor.
SOX9 can bind its own upstream activation site so its levels remain high even if SRY declines. This is a positive feedback mechanism.
SOX9 then acts to stimulate the expression of further downstream genes.
that will produce a Sertoli cell
(check ppt slide 4 for useful diagram)
What are the effects of SOX9? ie. how does it lead to gonadal development
- Stimulates production of prostaglandin D2 (PGD2) by the pre-Sertoli cells. PGD2 acts as a paracrine hormone to stimulate further SOX9 production in these cells. This second positive feedback mechanism serves to re-enforce all precursor cells along the sertoli pathway.
2.SOX9 stimulates production of fibroblast growth factor 9 (FGF9). FGF9 acts as a chemotactic factor for cell migration into the developing testis. It also further stimulates the production of SOX9 a third positive feedback mechanism.
- SOX9 stimulates the production of anti-Mullerian hormone (AMH). AMH causes the regression of the mullerian ducts which develop into the uterus and fallopian tubes in the female. (developing sertoli cells prod. AMH)
- Inhibition of female transcription factors WNT4 and FOXL2
What are the precursours for gonadal development
Their precursor is derived from common somatic mesenchymal tissue precursors called the genital ridge primordia (3½ - 4½ weeks) on posterior wall of lower thoracic lumbar region.
After fertilisation a pair of gonads develop which are bipotential. (Each duct can either become male or female genitalia)
For gonadal development what are the 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 hind gut, to the region of the developing kidney and on to the genital ridge – completed by 6 weeks.
describe the formation of primitive sex cords
Cells from the germinal epithelium that overlies the genital ridge mesenchyme migrate inwards as columns called the primitive sex cords.
in males: SRY expression
Penetrate medullary mesenchyme & surround primordial germ cells to form testis cords – precursor of seminiferous tubules.
Eventually become Sertoli Cells which express AMH.
in females: 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.
what do the invading cells become
In men:
primordial germ cells— spermatozoa
primitive sex cords— Sertoli cells (SRY, AMH)
mesonephric cells— leydic cells (testosterone)
In women :
Primordial germ cells: oocyte
primitive sex cord: Granulosa cells
Mesonephric cells: Theca cells
What are the internal reproductive organs?
The Mullerian duct:
most important for female
inhibited in the male by AMH
the Wolffian duct:
most important in the male stimulated by testosterone
lack of stimulation by testosterone means regression in female
Describe external differentiation
Testosterone is converted in the genital skin to the more potent androgen DHT (dihydrotestosterone) by 5-a-reductase.
DHT binds to the testosterone receptor, but is more potent than testosterone.
DHT causes differentiation of the male external genitalia:
Clitoral area enlarges into penis
Labia fuse and become ruggated to form scrotum
Prostate forms
Define Sex and gender
Sex
The biological aspects of an individual as determined by their anatomy, which is produced by their chromosomes & hormones etc
Gender
Defined as a social construction relating to behaviours and attributes based on labels of masculinity and femininity.
Define gender identity
The personal, internal perception of oneself. An individual may see themselves as a man, woman, as having no gender, or as having a non-binary gender, where people identify as somewhere on a spectrum between man and woman.
Define gender role
Expression or portrayal of psychological characteristics that are considered sexually dimorphic within the general population (eg. toy preferences / physical aggression etc).
