Normal Sex Differentiation Flashcards
What is sexual determination?
Genetically controlled process dependent on ‘switch’ on Y chromosome
Chromosomal determination of male or female.
What is sexual differentiation?
Process by which internal and external genitalia develop as male or female
Describe the relationship between sexual determination and differentiation
The two processes are contiguous and consist of several stages
Which gene is responsible for testicular formation?
SRY gene creates the testis
What is the result of Y chr. absence?
In the absence of Y chromosome ovaries develop
When does the SRY gene produce its effects?
Sex determining region Y (SRY) switches on briefly during embryo development (>week 7) to make gonad into a testis
Name the testicular cells and their hormone secretions
Sertoli cells: AMH
Leydig cells: Testosterone
What are the effects of testicular hormone release?
Products of testis influence further gonadal and phenotypic sexual development
Describe the structure and function of SRY gene
SRY is a DNA binding protein that acts as a transcription factor
What transcription factors are responsible for testis formation?
SRY and SOX9 are TF that turn OFF genes promoting ovarian development
Where does DNA bind during testis formation?
Critical site of DNA binding is upstream of SOX9
How is SOX9 activated?
SOX9 can bind own upstream activation site = levels remain high even if SRY declines.
+ve feedback mechanism.
What are the effects of SOX9 activation?
SOX9 acts to stimulate expression of further downstream genes ==> become Sertoli cell
Describe the relationship between SRY and SOX9
SRY determines executive policy and SOX9 implements it
What are the 4 mechanisms of SOX9 action?
- PDG2 production
- FGF9 production
- AMH production
- Female TF WNT4 / FOXL2 inhibition
How does SOX9 stimulate PDG2 secretion?
Via pre-sertoli cells
What is the effect of SOX9 PGD2 secretion?
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
What are the effects of SOX9 FGF9 production?
Acts as a chemotactic factor for cell migration into developing testis.
Further stimulates SOX9 production
> 3rd +ve feedback mechanism
Describe the effects of SOX9 AMH production
AMH causes regression of the mullerian ducts which develop into uterus and fallopian tubes in females
What occurs in the absence of SRY gene?
In the absence of SRY, WNT4 and FOXL2 are stimulated.
FOXL2 inhibits SOX9
Where do gonads develop from?
Gonadal precursor derived from common somatic mesenchymal tissue precursors
==> Genital ridge primordia (develops at 3½ - 4½ weeks)
Name the 3 waves of cells that invade the genital ridge
- Primordial Germ cells (sperm / oocytes)
- Primitive Sex cords - sertoli (M) / granulosa (F)
- Mesonephric cells - blood vessels and Leydig (M) / Theca (F) cells
What initiates primordial germ cell migration?
A small cluster of cells in yolk sac epithelium expands by mitosis at ~3 weeks.
Describe the primordial germ cell migration
PGC migrate to connective tissue of hind gut
move to region of developing kidney and on to genital ridge
– completed by 6 weeks.
Describe the formation of the primitive sex cords
Cells from germinal epithelium overlying the genital ridge mesenchyme migrate inwards as columns = primitive sex cords
Where do mesonephric cells originate?
Originate in mesonephric primordium - lateral to genital ridges
What influences male mesonephric cell formation?
Act under influence of pre-sertoli cells (express SRY)
What do male mesonephric cells form?
Vascular tissue
Leydig cells
- make testosterone, don’t express SRY
Basement membrane
– contributes to formation of seminiferous tubules and rete-testis
What do female mesonephric cells produce?
Without SRY influence:
- Vascular tissue
- Theca cells
What do theca cells produce?
Theca cells produce androgens in adult life but not at embryonic stage
What do the mullerian ducts form?
uterus, uterine tubes, upper ⅓ of vagina and cervix
What do the wolffian ducts form?
vas deferens, seminiferous tubules and epididymis
Describe the effects of testosterone on wolffian ducts
Stimulated by testosterone
lack of stimulation by testosterone means regression in female
Describe the effect of AMH in males
AMH causes mullerian regression in males
Where is testosterone converted to DHT?
Testosterone is converted in the genital skin to the more potent androgen DHT (dihydrotestosterone) by 5-a-reductase
Where does DHT bind?
DHT binds to the testosterone receptor, but is more potent than testosterone
What are the effects of DHT binding?
DHT causes differentiation of the male external genitalia
Outline the development of male genitalia due to DHT
- Clitoral area enlarges into penis
- Labia fuse and become ruggated to form scrotum
- Prostate forms
Outline the external differentiation of male genitalia
DHT presence
- genital tubercle becomes fallace → glans penis
- Urethral fold folds in on itself to form hollow tube
- Genital swelling becomes scrotal swelling; rugated
Describe female external genitalia differentiation
DHT Absence
- gential tubercle becomes clitoris
- Urethral fold becomes vaginal opening
- genital swelling becomes labia minora and majora
How are gender attributes assigned?
Based on attitudes, expectations, behaviours or roles - may be highly complex
What is gender identity?
self-representation or identification as male or female (or neither)
What is a gender role?
expression of psychological characteristics considered sexually dimorphic within general population
e.g. toy preferences / physical aggression etc.
What is a sexual orientation?
refers to choice of sexual partner and erotic interest
e.g. include heterosexual, bisexual, homosexual
What is psychosexual neutrality?
The view that gender assignment of a newborn with ambiguous genitalia can be made regardless of endocrine history
What is neural bias?
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
How does the amygdala size differ in males and females?
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
What is the role of the maygdala?
Brain region involved in emotional processing
How does the hippocampus differ amongst genders?
Hippocampus contains more grey matter in females - involved in memory & social cognition
