Sexual differentiation Flashcards
Prevalence of genital abnormalities
1 in 4500
Sex determination
Occurs during fertilisation
X or Y chromosome is inherited from father.
X chromosome inherited from mother.
XY- male
XX- female
Origin of primordial germ cells
Arise from the epiblast are week 2
- Pluripotent cells
Differentiation of primordial germ cells
Firstly migrates to yolk sac
- Prevents imprinting
Later returns next to genital ridge (next to kidneys)
- Indifferent gonad
XX- replicate at cortex
XY- replicate at medulla
Gender decision is dependant on genetic switches and hormones
Genetic switches
Transcription factors
- Wt1, Sf1
Specific promoters of testis development
Specific promoters of ovarian development
Specific promoters of testis development
A type of genetic switch that determines the male sex.
Examples
- Sry
- Sox9
Supporting cell precursors
Bipotential gonad cells that originate from the urogenital ridge
Differentiates into
- Follicular cells in ovaries
- Sertoli cells in testis
Primordial germ cells
Bipotential gonad cells that originate from the epiblast
Differentiates into
- Oocytes in ovaries
- Pro-spermatogonia cells in testis
Steroidogenic precursor cells
Bipotential gonad cells from the urogential ridge
Differentiates into
- Internal theca cells in ovaries
- Leydig cells in testis
Differentiation of sex cord cells in females
Differentiates into granulosa in ovaries
- Supports and nutrifyes the ovum
Differentiation of the cortex in females
Forms layer of theca cells
- Secretes androgens
Sry
Specific genetic promoter of testis development.
Influences definition and identity of Sertoli cells
- Stimulates AMH secretion.
AMH
Anti-mullerian hormone
Produced from sertoli cells under the influence of Sry gene
- Suppresses female development pathway
- Induces Leydig differentiation (from intermediate mesoderm)
Origin of kidney
Intermediate mesoderm
- Between somites and lateral plate
Pronephros
First stage of kidney development
- Disappears right after formation
Mesonephros
Structure formed in the second stage of kidney development
Leaves ducts before degeneration
- Ducts become integral part of the reproductive system
Metanephros
Final stage of kidney development that fully develops into the kidney
Time of internal genital organs differentiation
Week 8
Origin of internal genitial organs
All embryos contain two sets of paired ducts at the start
- Paramesonephric–> Mullerian
- Mesonephric—> Wolffian
Mullerian duct
Kept in the female embryo
- Due to the absence of anti-Mullerian hormone
The duct is composed of:
- Oviduct
- Uterus
- Cervix
- Upper vagina
Differentiation of the male genital organs
In the male embryo, AMH and male hormones are secreted
- AMH regresses the mullerian/ paramesonephric duct
- Testosterone promotes Wolffian duct differentiation
Wolffian duct
Composed of
- Epididymis
- Vas deferens
- Seminal vesicle
Genital tubercle
Initial development of external genital organs in both sexes
Both show an elevated midline swelling.
Composed of
- Urethral groove
- Paired urethral folds
- Paired labioscrotal swellings
Development of male external genital organs
Some testosterone—> DHT
DHT stimulates the development of:
- Urethra (spongy urethra from urethral fold fusion)
- Prostate
- Scrotum (from labioscrotal swellings)
- Penis (from genital tubercle)
Development of female external genital organs
No DHT stimulates:
- Clitoris (from genital tubercle)
- Labia minora (from open urethral fold)
- Labia majora (labioscrotal swelling)
- Vestibule (from urethral groove)
Turner’s syndrome
- Genetics
- Prevalence
- Prognosis of embryos
- Diagnosis
Monosomy
- XO
1:2500 females
99% of embryos are not viable
Diagnosed by assessing karyotype from amniocentesis
Turner’s syndrome
- Clinical presentation [6]
Short stature
- Low oestrogen
Underdeveloped gonads
Webbed neck
Failure to undergo puberty/ menstruation
Constricted aorta
Shorter metacarpal IV/ small finger nails
Klinefelter’s syndrome
- Genetics
- Prevalence
- Diagnosis
47 XXY
1:600-1000 male births
Appear normal at birth
- Diagnosed via karyotyping (amniocentesis)
Klinefelter’s syndrome
- Presentation
Tall height
- Excess oestrogen
Reduced facial/body hair
Gynaecomastia
Osteoporosis
Feminine fat distribution
Testicular atrophy
True hermaphrodite
- Description’
- Genetics
- Possible cause
Rare condition where an individual is born with ovarian and testicular tissue. Genital may be - Ambigous - Male/ female Genetics - 46 XX (SRY+) - 45 X (SRY +) - 45 X
Cause
- Two ova fertilised by two sperm and fused
Female pseduohermaphrodite
46 XX with virilization
- Excess androgens
Normal internal genital organs
Male external appearance and genitals
Fusion of labia, large clitoris
Possible cause
- XS androgen exposure during pregnancy (i.e in CAH)
Male pseduohermaphrodite
- Genetics
- External genitalia
- Testis
- Other features
46, XY with undervirilization
External genital
- Incomplete/ ambiguous/ female
Other features
- Blind-ending vagina
- No breast
- Primary amenorrhea
Testis
- Normal/ malformed/ absenct
Male pseduohermaphrodite
- Main causes
Defective androgen synthesis in utero
Defective androgen action (receptor disorder)
Androgen insensitivity syndrome
- Other name
- Prevalence
- Description
Known as testicular feminization
1:20000-64000 male births
Dysfunction receptor to male hormones
Leydig cell hypoplasia
Possibly caused by insensitivity to LH
Leydig cells do not produce LH
Features
- External genitalia female/ slightly ambigous
- No female internal genitalia
XY gonadal dysgenesis
Also known as Swyer’s syndrome
- Sry gene alteration
External- female
No functional gonads
- No testicular differentiation
- No menstruation
- May develop into malignancy
Unicornuate uterus
Congenital mullerian anomaly
Only connected to one fallopian tube+ ovary
- Endometrial space is halved.
Cryptotchidism
- Description
- Prevalence
Undescended testis
- Can be unilateral/ bilateral
-30% premature males, 3-4% term males
Undescended ovaries
Much less common than cryptochidism
Detected with clinical fertility assessment
Male hypospadia
- Description
- Prevalence
Failure of male urogenital folds to fuse
- Proximal displaced urethral meatus
1:125 male births
Sexual behaviour
Gene expression is important in acquiring gender identity
- Inactivation of genes from x chromosome showed predisposition to transexualism in animal studies.
Gene expression in brain takes place way before gonadal development (Week 2)
Differing gene expression in male and female brain
Mouse embryos showed 51 genes different between male and female
- Active genes before gonads develop (week 2)
