Normal Sexual Differentiation Flashcards

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1
Q

Sexual Determination

A

Genetically controlled process dependent on the ‘switch’ on the Y chromosome.

Chromosomal determination of male & female.

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2
Q

Sexual Differentiation

A

The process by which internal and external genitalia develop as male or female

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3
Q

SRY gene creates ________

A

The testis

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4
Q

Absence of Y Chromosome

A

Ovaries

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5
Q

What is SRY (Sex Determining Region)

A

Transcription Factor

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6
Q

When does SRY switch on?

A

Switches briefly on during early development (>week7)

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7
Q

What does SRY switched on, make?

A

Gonad -> Testis -> Cells -> Hormones

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8
Q

Testis Develop and Form which two cells?

A

Sertoli and Leydig cells

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9
Q

Sertoli cells produce…

A

AMH (anti-mullarian hormone)

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10
Q

Leydig cells produce…

A

Testosterone

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11
Q

Picture of one chromosome:

Euchromatin and Heterochromatin

Pseudoatosomal Region

A
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12
Q

Mechanism of SRY action

SOX 9’s first positive feedback mechanism?

A

SOX9 can bind its own upstream activation site so its levels remain high even if SRY declines.

This is a positive feedback mechanism.

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13
Q

Mechanism of SRY action

SOX9 activation stimulates production of?

and by what?

A

Stimulates production of prostaglandin D2 (PGD2) by the pre-sertoli cells.

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14
Q

Mechanism of SRY action - How does SOX9 achieve its effects?

What does PGD2 act as?

A

Acts as a paracrine hormone to stimulate further SOX9 production in these cells.

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15
Q

Mechanism of SRY action - How does SOX9 achieve its effects?

SOX-9 stimulates production of?

A

SOX9 stimulates production of fibroblast growth factor 9 (FGF9).

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16
Q

Mechanism of SRY action - How does SOX9 achieve its effects?

FGF-9 acts as a _____

It further stimulates what?

A

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.

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17
Q

Mechanism of SRY action - How does SOX9 achieve its effects?

SOX-9 also stimulates production of?

A

anti-Mullerian hormone (AMH).

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18
Q

Mechanism of SRY action - How does SOX9 achieve its effects?

AMH causes the regression of the…⠀⠀⠀⠀⠀

A

mullerian ducts

which develop into the uterus and fallopian tubes in the female!

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19
Q

Mechanism of SRY action - How does SOX9 achieve its effects?

SOX9 inhibits the production of female transcription factors:⠀

A

Female Transcription Factors

WNT4 & FOXL2

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20
Q

Bipotential meaning

A

Gonads that can develop into either male or female

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21
Q

Where do the precursors of bipotential gonads come from? and what are they called?

A

common somatic mesenchymal tissue precursors called the genital ridge primordia

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22
Q

When approximately does this genital ridge primordia region appear?

A

(3½ - 4½ weeks)

23
Q

Where is this anatomically located:

Common somatic mesenchymal tissue precursors called the genital ridge primordia

(3½ - 4½ weeks)

A

Posterior wall of lower thoracic lumbar region

24
Q

Genital Ridge (3 waves of cells invade gential ridge)

1) Primordial Germ cells become either?

A

Sperm or Oocytes

25
Q

Genital Ridge (3 waves of cells invade gential ridge)

1) How do Primordial Germ cells become sperm or oocytes?

A
  • Small Cluster of cells in epithelium of yolk expand by mitosis (~3 weeks)
  • They then migrate to:
    *connective tissue of hind gut
    *region of developing kidney
    *onto Genital ridge waiting for signal

(completed by week 6)

26
Q

Genital Ridge (3 waves of cells invade gential ridge)

2) Primitive Sex Cords become either?

A

Sertoli (male ) or Granulosa cells (female)

27
Q

Genital Ridge (3 waves of cells invade gential ridge)

2) How are primative sex cords formed?

A

Cells from the germinal epithelium that overlied the genital ridge mesenchyme migrate inwards as columns called the primitive sex cords!

28
Q

Genital Ridge (3 waves of cells invade gential ridge)

2) Male Summary

A

SRY expression

Penetrate medullary mesenchyme & surround primordial germ cells to form testis cords – precursor of seminiferous tubules.

Eventually become Sertoli Cells which express AMH.

29
Q

Genital Ridge (3 waves of cells invade gential ridge)

2) Female Summary

A

No SRY

Sex cords ill defined and do not penetrate deeply

Instead, they condense in the cortex as small clusters around primordial germ cells – precursor of ovarian follicle

Eventually become Granulosa cells.

30
Q

Genital Ridge (3 waves of cells invade gential ridge)

3) Mesonephric Cells become?

A
  • Blood vessels
  • Leydig cells (male)
  • Theca cells (female).
31
Q

Genital Ridge (3 waves of cells invade gential ridge)

3) Where do Mesonephric Cells originate from?

A

The mesonephric primordium which are just lateral to the genital ridges.

32
Q

Genital Ridge (3 waves of cells invade gential ridge)

3) In males, Mesonephric Cells act under the influence of?

A

pre-sertoli cells (which themselves express SRY)

33
Q

Genital Ridge (3 waves of cells invade gential ridge)

3) The pre-sertoli cells form 3 things, what are they?

A
  • Vascular tissue
  • Leydig cells (synthesize testosterone, do not express SRY)
  • Basement membrane – contributing to formation of seminiferous tubules and rete-testis
34
Q

Genital Ridge (3 waves of cells invade gential ridge)

3) In females, the cells without the influence of SRY they form:

A
  • Vascular tissue
  • Theca cells
35
Q

Mullerian Duct will grow regardless unless?

A

Inhibited by AMH

36
Q

Wollfian Duct is stimulated by?

A

Testosterone

37
Q

Genital Ridge picture

A

Purple

38
Q

Where is testosterone converted to DHT?

A

At the genital skin

39
Q

What is the enzyme responsible for testosterone conversion into DHT?

A

5-a-reductase

40
Q

What is Testosterone converted to in the genital skin?

A

Testosterone is converted in the genital skin to the more potent androgen DHT (dihydrotestosterone) by 5-a-reductase.

41
Q

How does DHT causes differentiation of the male external genitalia? (Give specific examples)

A
  • Clitoral area enlarges into penis
  • Labia fuse and become ruggated to form scrotum
  • Prostate forms
42
Q

Sex differentiation summary

A

You got this!

43
Q

Events in Sex Differentiation with Foetal age

A
44
Q

What happens at week 4 Foetal age?

A

1) Wolfian Duct development
2) (Week ~4.5) Genital ridge

45
Q

What happens at week 5 Foetal age?

A

Primordial Germ Cell migration

46
Q

What happens at week 6 Foetal age?

A

Mullerian Duct development

47
Q

What happens at week 7 Foetal age?

A

Seminiferous tubules

48
Q

What happens at week 8 Foetal age?

A

-AMH made so Mullerian regress in male

-Leydig cells

49
Q

What happens at week 9 Foetal age?

A

First signs of vagina

First meiotic prophase in oogonia

50
Q

What happens at week 10 Foetal age?

A

Begin masculinisation of external genitalia

Prostatic buds

Begin regression of Wolffian Duct in female

Testis begins migration

51
Q

What happens at week 12-14 Foetal age?

A

Penis developed

52
Q

What happens at week 17 Foetal age?

A

First follicles

53
Q

What happens at week 24 Foetal age?

A

Vagina developed