Normal sexual differentiation Flashcards
sexual determination
genetically controlled process dependent on the switch on the Y chromosome, determination of male or female.
sexual differentiation
process by which internal and external genitalia develop as males or females.
SRYgene
- on the y chromosome
- when this gene is switched on testis develop at week 7
-in the absence of Y chromosome = no SRY gene so ovaries develop.
What are the cells of testis and what 2 hormones do they make?
- Leydig - makes testosterone
- Sertoli - produce AMH
=> production of these two hormones influences further development of gonodal phenotypic features.
What is SOX9?
- SRY is a DNA binding protein that acts as a transcription factor and bind to SOX9 to turn it on.
-SOX9 is also a transcription factor
-Binding of SRY to SOX9 stimulates the turning on of testicular genes and turning off ovarian genes to develop a foetus into a male.
Why can SOX9 work even in the absence of SRY?
SOX9 is independent of SRY bc it can produces fibroblast growth factors which enhances sox9 production , it is autocrine and bind to its own upstream activation site so its levels remain high (positive mechanism).
How does SOX9 achieve its effects?
- stimulates production of prostaglandin D2 (PGD2) by the pre-sertoli cells.
- PGD2 acts as a paracrine hormone to stimulate further production pof SOX9 in these pre-sertoli cells (second positive feedback).
- SOx9 stimulates the production of anti- Mullerian (AMH). AMH causes the regression of the mullerian ducts which develop into the uterus and fallopian tubes in the female developing into male testis
- Inhibition of female transcription factors WNT4 and FOXL2 thus developing into male testis
Transcriptional pathway in serotoli cell
mechanism pathway in the granulosa cell
When do gonads develop?
-after fertilisation a pair of gonads develop which are bipotential
what tissue is the precursor of gonads derived from and where?
-common somatic mesenchymal tissue precursors called genitial ridge primordial (3 to 4 weeks)
-in the posterior wall of lower thoracic lumbar region.
what 3 waves of cells invade the genital ridge?
1.primordial germ cells
2. primitive sex cords
3. mesenpheric cells
primordial germ cells
-initially small cluster of cells in the epithelium of yolk sac expands by mitosis aroun 3 weeks
primitive cord
-cells from germinal epithelium that overlies the genital ridge mesenchyme migrate inwards as columns called primitive sex cords
- females = no SRY expressed, no deep penetration of sex cords, follicle formed and granulosa cells
-males = SRY expressed, develop testis cords and seminiferous vesicles and Sertoli cells
mesenpheric cells
- occur in mesenephric primordium which are lateral to the genital ridges
-males : act under influence pf pre-sertoli (which express SRY) cells to form leydig cells, basement membrane, vascular tissue
-females: without influence of SRY they form vascular tissue, and theca cells.
What are female internal reproductive ducts?
Mullerian ducts:
- most important in females
-inhibited in males by AMH
What are male internal reproductive ducts?
wolfian ducts
- stimulated by testosterone
-lack of stimulation by testosterone in female leads to regresssion of the duct.
What hormone is involved in the external genital differentiation?
-5 alpha-reductase
-testosterone => dihydrotestosterone (DHT) by this enzyme
-dihydrotestosterone is what causes the differntiation of external male genitalia
How does DHT lead to differentiation of male genitalia
-DHT is more potent than testosterone and binds to testosterone receptors with higher affinity, causing differentiation of male genitalia:
1. clitoris area enlarges to penis
2. labia fuse and become ruggated from scrotum
3. prostate forms.
Sex differentiation summary
how is hormones and behaviour linked?
exposing animals to sex hormones during critical period before or just after birth is associated with sexual divergent (different sexes)
Nature: gender differences in the brain
-numerous genes are differentially expressed in males and female embryonic brains
-both morphological and functional differences in human brain structure according to sex have been found :
1. amygdala larger in males - which correlates with increased aggressive behaviour in males.
2. left amygdala larger in females - region associated with emotions
3. hippocampus contains more grey matter in females :
involved in memory and social cognition
4. third intersitial nucleus of the anterior hypothalamus (INAH-3) has been suggested to be a major determinant of sexual identity. may be larger in heterosexual males than homosexual males and heterosexual females.
How can you interpret a functional MRI (fMRI)
-increased activity in certain regions of brain , more oxygen used so more blood flow appears red.
-neuroimaging has shown functional sex differences in a variety of brain regions when subjects undergone activities related to emotion, memory , language etc.
- evidence of certain bilateral differences between two genders
Nurture : social learning
when adults are handed a baby and they are told the baby is a boy or a girl the way they play with it is different.
study : adults were asked to watch a film of a child at play, half were told it was a girl and other half told it was a boy.
findings: those who were told it was a boy thought the baby was angry when it was startled whereas those who though it was a girl thought the baby showed signs of distress.
