Lecture 21 - 2018/2017 Flashcards
What are the levels of sexual differentiation?
- Gonads.
- Internal genitalia.
- External genitalia.
When do the bipotential gonads develop?
<6 weeks.
When do bipotential internal genitalia develop?
<7 weeks.
When do bipotential external genitalia develop?
<8 weeks.
What determines male internal and external sexual differentiation?
Testis. An ovary or no gonad will result in female internal and external genitalia.
Describe gonadal development?
The gonad is equivalent to the formation of the genital ridge - it will arise as a paired structure in the intermediate mesoderm.
What are the genital ridges (from anterior to posterior)?
- Pronephros - caudal end forms adrenals.
- Mesonephros - central region forms the gonads and internal reproductive structures (wolffian - male; mullerian - female).
- Metanephros - posterior end forms the kidneys.
What is the development of the genital ridge dependent on?
Activation of nuclear transcription factors.
What do these transcription factors do?
These proteins bind and form part of the protein complex around DNA altering gene transcription/expression.
What happens if there is a mutation in these transcription factors?
Development of gonadal and renal organogenesis occurs from similar transcription factors, as organogenesis occurs from the genital ridge. Mutations in these transcription factors can affect more than one organ system i.e. kidney or adrenal glands.
What are the genes involved in human gonadal development?
- Insulin Like Growth Factor 1 Receptor (IGFR1).
- Wilms Tumour (WT1).
- Steroidigenic Factor 1 (SF1).
- DAX1.
What happens if there is a loss of function of the genes?
No gonads will form (no gonads is female - default mode is female).
What initiates testicular determination?
SRY - sex determining region of Y.
Where is the SRY gene found?
Pre-sertoli cells.
What does SRY do?
Up-regulates SOX-9 gene.
Describe male gonadal determination?
SF1 initiates the transcription of SOX-9. SRY will up-regulate SOX-9. SOX-9 then up-regulates itself (positive feedback loop) and stimulates prostaglandin D and FGF-9.
What do SOX-9, Prostaglandin D and FGF-9 do?
Inhibit ovarian transcription factors.
Describe leydig cell determination?
Leydig cells arise from within the interstitum of the testis outside the chord. They provide the steroidogenic function of the testis. Initial fetal leydig cells regress and are replaced by adult leydig cell post natally.
What are the functions of the ovaries?
- Production of steroid hormone.
2. Generation of mature oocytes capable of being fertilised.
When do ovarian follicles commence differentiation?
After birth.
Does the ovary affect internal or external genitalia development?
No.
Where do primordial germ cells arise from?
Allantois (yolk sac).
The primordial germ cell survival during migration is dependent on what?
c-KIT/Steel Factor (Stem Cell Factor) - may use a concentration gradient to migrate down.
What happens one the primordial germ cells are inside the genital ridge?
The cells lose mobility and aggregate together. In the testis germ cells enter cords and have mitotic arrest. In the ovaries, germ cells continue into early meiosis before arresting.
