Normal Sex Differentiation

Question 1

What is sexual determination?

Answer 1

Genetically controlled process dependent on ‘switch’ on Y chromosome

Chromosomal determination of male or female.

Question 2

What is sexual differentiation?

Answer 2

Process by which internal and external genitalia develop as male or female

Question 3

Describe the relationship between sexual determination and differentiation

Answer 3

The two processes are contiguous and consist of several stages

Question 4

Which gene is responsible for testicular formation?

Answer 4

SRY gene creates the testis

Question 5

What is the result of Y chr. absence?

Answer 5

In the absence of Y chromosome ovaries develop

Question 6

When does the SRY gene produce its effects?

Answer 6

Sex determining region Y (SRY) switches on briefly during embryo development (>week 7) to make gonad into a testis

Question 7

Name the testicular cells and their hormone secretions

Answer 7

Sertoli cells: AMH

Leydig cells: Testosterone

Question 8

What are the effects of testicular hormone release?

Answer 8

Products of testis influence further gonadal and phenotypic sexual development

Question 9

Describe the structure and function of SRY gene

Answer 9

SRY is a DNA binding protein that acts as a transcription factor

Question 10

What transcription factors are responsible for testis formation?

Answer 10

SRY and SOX9 are TF that turn OFF genes promoting ovarian development

Question 11

Where does DNA bind during testis formation?

Answer 11

Critical site of DNA binding is upstream of SOX9

Question 12

How is SOX9 activated?

Answer 12

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

+ve feedback mechanism.

Question 13

What are the effects of SOX9 activation?

Answer 13

SOX9 acts to stimulate expression of further downstream genes ==> become Sertoli cell

Question 14

Describe the relationship between SRY and SOX9

Answer 14

SRY determines executive policy and SOX9 implements it

Question 15

What are the 4 mechanisms of SOX9 action?

Answer 15

1. PDG2 production
2. FGF9 production
3. AMH production
4. Female TF WNT4 / FOXL2 inhibition

Question 16

How does SOX9 stimulate PDG2 secretion?

Answer 16

Via pre-sertoli cells

Question 17

What is the effect of SOX9 PGD2 secretion?

Answer 17

PGD2 acts as a paracrine hormone to stimulate further SOX9 production in pre-sertoli cells
2nd +ve feedback ensures all precursor cells commit to sertoli cell pathway

Question 18

What are the effects of SOX9 FGF9 production?

Answer 18

Acts as a chemotactic factor for cell migration into developing testis.

Further stimulates SOX9 production

> 3rd +ve feedback mechanism

Question 19

Describe the effects of SOX9 AMH production

Answer 19

AMH causes regression of the mullerian ducts which develop into uterus and fallopian tubes in females

Question 20

What occurs in the absence of SRY gene?

Answer 20

In the absence of SRY, WNT4 and FOXL2 are stimulated.

FOXL2 inhibits SOX9

Question 21

Where do gonads develop from?

Answer 21

Gonadal precursor derived from common somatic mesenchymal tissue precursors

==> Genital ridge primordia (develops at 3½ - 4½ weeks)

Question 22

Name the 3 waves of cells that invade the genital ridge

Answer 22

1. Primordial Germ cells (sperm / oocytes)
2. Primitive Sex cords - sertoli (M) / granulosa (F)
3. Mesonephric cells - blood vessels and Leydig (M) / Theca (F) cells

Question 23

What initiates primordial germ cell migration?

Answer 23

A small cluster of cells in yolk sac epithelium expands by mitosis at ~3 weeks.

Question 24

Describe the primordial germ cell migration

Answer 24

PGC migrate to connective tissue of hind gut

move to region of developing kidney and on to genital ridge

– completed by 6 weeks.

Question 25

Describe the formation of the primitive sex cords

Answer 25

Cells from germinal epithelium overlying the genital ridge mesenchyme migrate inwards as columns = primitive sex cords

Question 26

Where do mesonephric cells originate?

Answer 26

Originate in mesonephric primordium - lateral to genital ridges

Question 27

What influences male mesonephric cell formation?

Answer 27

Act under influence of pre-sertoli cells (express SRY)

Question 28

What do male mesonephric cells form?

Answer 28

Vascular tissue

Leydig cells
- make testosterone, don’t express SRY

Basement membrane
– contributes to formation of seminiferous tubules and rete-testis

Question 29

What do female mesonephric cells produce?

Answer 29

Without SRY influence:

• Vascular tissue
• Theca cells

Question 30

What do theca cells produce?

Answer 30

Theca cells produce androgens in adult life but not at embryonic stage

Question 31

What do the mullerian ducts form?

Answer 31

uterus, uterine tubes, upper ⅓ of vagina and cervix

Question 32

What do the wolffian ducts form?

Answer 32

vas deferens, seminiferous tubules and epididymis

Question 33

Describe the effects of testosterone on wolffian ducts

Answer 33

Stimulated by testosterone

lack of stimulation by testosterone means regression in female

Question 34

Describe the effect of AMH in males

Answer 34

AMH causes mullerian regression in males

Question 35

Where is testosterone converted to DHT?

Answer 35

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

Question 36

Where does DHT bind?

Answer 36

DHT binds to the testosterone receptor, but is more potent than testosterone

Question 37

What are the effects of DHT binding?

Answer 37

DHT causes differentiation of the male external genitalia

Question 38

Outline the development of male genitalia due to DHT

Answer 38

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

Question 39

Outline the external differentiation of male genitalia

Answer 39

DHT presence
- genital tubercle becomes fallace → glans penis

• Urethral fold folds in on itself to form hollow tube
• Genital swelling becomes scrotal swelling; rugated

Question 40

Describe female external genitalia differentiation

Answer 40

DHT Absence
- gential tubercle becomes clitoris

• Urethral fold becomes vaginal opening
• genital swelling becomes labia minora and majora

Question 41

How are gender attributes assigned?

Answer 41

Based on attitudes, expectations, behaviours or roles - may be highly complex

Question 42

What is gender identity?

Answer 42

self-representation or identification as male or female (or neither)

Question 43

What is a gender role?

Answer 43

expression of psychological characteristics considered sexually dimorphic within general population

e.g. toy preferences / physical aggression etc.

Question 44

What is a sexual orientation?

Answer 44

refers to choice of sexual partner and erotic interest

e.g. include heterosexual, bisexual, homosexual

Question 45

What is psychosexual neutrality?

Answer 45

The view that gender assignment of a newborn with ambiguous genitalia can be made regardless of endocrine history

Question 46

What is neural bias?

Answer 46

Idea that a tendency for male or female is already present in neonates as a result of prenatal factors such as hormonal milieu in utero

Question 47

How does the amygdala size differ in males and females?

Answer 47

Amygdala larger in males
- size positively correlated with aggressive behaviour across species

Left amygdala more active in women - emotional memories.

Right amygdala more active in men - action

Question 48

What is the role of the maygdala?

Answer 48

Brain region involved in emotional processing

Question 49

How does the hippocampus differ amongst genders?

Answer 49

Hippocampus contains more grey matter in females - involved in memory & social cognition