How to make a boy or a girl Flashcards
What is the prevalence of genital abnormalities
1/4500
Making a boy/girl involved 3 main events
Describe the sex determination, during fertilisation
- Inheritance of X or Y from father
- At week 2 primordial germ cells (PGCs) arise from the epiblast
- PGCs are pluripotent
- PGC’ migrate to yolk sac stalk to avoid becoming imprinted. They later return travelling to the genital ridge (next to the kidney) and become the indifferent gonad
Making a boy/girl involved 3 main events
Describe the differentiation of gonad, week 5
- At genital ridge: XX PGCs replicate at cortex; XY PGCs replicate at the medulla
- Gonad gender decision relies on genetic switches and hormones
Genital transcription factors: Wt1, Sf1
Specific promoters of testis development: Sry,Sox9
Specific promoters of ovarian development: Wnt-4, FoxL2
At the urogenital ridge, bipotential gonad can either become a future ovary or a future testis. Which cells/precursors give rise to female
FUTURE OVARY
Supporting cell precursors –> follicular cells
Primordial germ cells –> oocytes
Steroidogenic precursors –> internal theca cells
Female PGCs –> oogonia (primary oocytes)
Sex cord cells–> granulosa (support and nutrify ovum)
Cortex –> layer of thecal cells –> secrete androgens before those generated by the follicles
At the urogenital ridge, bipotential gonad can either become a future ovary or a future testis. Which cells/precursors give rise to male
FUTURE TESTIS
Supporting cell precursors –> sertoli cells
Primordial germ cells –> pro-spermatogonia
Steroidogenic precursors –> leydig cells
Male PGCs–> spermatononica
Sry influences definition and identity of sertoli cells –> secretion of AMH (AMH suppresses female development pathway and induces cells in intermediate mesoderm to become leydig –> secrete testosterone)
Gonads are indifferent at start and linked to kidney development
Describe the origin, location and stages of kidney development
Origin: intermediate mesoderm (as the reproductive organs)
Location: between the somites and lateral plate (each side of the aorta)
Pronephros- diseappears soon after
Mesonephros - leaves remnants: ducts that become integral part of the reproductive system
Metanephros- becomes kidney
Making a boy/girl involved 3 main events
Describe the differentiation of internal and external genital organs, after week 5
Begin differentiation at week 8, formed from a priori identical primordium structures
Embryos at both sexes possess two sets of paired ducts at the start
- Paramesonephric (mullerian)
- In female embryo mullerian duct is kept due to the absence of AMH. Mullerian duct becomes oviduct, uterus, cervix, upper part of vagina
- In male embryo AMH causes mullerian duct regression and testosterone promotes wolffian duct differentiation - Mesonephric (Wolffian)
- Becomes epididymis, vas deferens and seminal vesicle
Why might an early embryo appear sexually ambiguous?
Both sexes show an elevated midline swelling - genital tubercle. This tubercle consists of
- urethral groove (opening into the urogenital sinus)
- paired urethral folds
- paired labioscrotal swellings
How does the indifferent stage differentiate into male sex organs
- Some testosterone is converted into DHT
DHT stimulates development of the urethra, prostate and external genitals (scrotum and penis) - Genital tubercle –> PENIS
- Fusion of the urethral folds –> spongy urethra
- Labioscrotal swellings –> scrotum
How does the indifferent stage differentiate into female sex organs
Absence of DHT
- Genital tubercle –> clitoris
- Urethral folds remain open -> labia minora
- Labioscrotal swellings –> labia majora
- Urethral groove –> vestibule
Turners syndrome is caused by a chromosomal abnormality
Describe its genetics, overall presentation and diagnosis
- Monosomy, XO
- 1: 2500 (females only)
- 99% non viable embryos
- Survivors fail to sexually mature at puberty and exhibit several physical abnormalities
- Diagnosis by amniocentesis
Turners syndrome is caused by a chromosomal abnormality
State 5 clinical signs
- Short stature
- Large carrying angle (elbow deformity)
- Low hairline
- Folds of skin
- Coarctation of the aorta
- Shield shaped thorax
- Widely spaced nipples
- Shortened metacarpal 4
- Small finger nails
- Poor breast development
- Brown spots
- No menstruation
Klinefelters syndrome is caused by a chromosomal abnormlity
Describe its genetics and overall presentation
- Affects chromosome 47, XXY
- 1 in every 600-1000 male births
- Appear normal at birth, diagnosis confirmed through amniocentesis
- Become infertile and exhibit some features associated with female development (e.g. gynecomastia)
Klinefelters is caused by a chromosomal abnormality
State 5 clinical signs
- Taller than average
- Reduced facial hair
- Reduced body hair
- Breast development (gynaecomastia)
- osteoporosis
- feminine fat distribution
- small testes (testicular atrophy)
Describe true hermaphroditism
Think about chromosomal effect, possible cause and internal and external reproductive organs
EXTREMELY RARE
- born with both ovarian and testicular tissue (ovotestis) - ambiguous genitalia due to a complicated mosaic karyotype
- 46XX (SRY+), 45X (SRY+), and 45X
- possible cause: two ova fertilised by two sperm that fuse to form a tetragametic chimera
- external genital may be ambiguous or appear one gender
Describe female pseudohermaphroditism
Think about chromosomal effect, possible cause and internal and external reproductive organs
- 46XX with virilisation (due to androgens)
- internal sex organs are normal includingovarues
- external appearance and genitals: male
- features: fusion of labia and enlarged clitoris
- possible cause: exposure to male hormones prior to birth (e.g. from congenital virilising adrenal hyperplasia_
Describe male pseudohermaphroditism
Think about chromosomal effect, possible cause and internal and external reproductive organs
- 46 XY with undervirilisation
- External genitals: incompletely formed, ambiguous or clearly female
- May have blind-ending vagina, absence of breast development, primary amenorrhoea
- Testis can be normal, malformed or absent
- Main causes: defective androgen synthesis, defective androgen action (e.g. receptor disorder), AIS, Leydig cell hypoplasia
What is androgen insensitivity syndrome (AIS)
AKA Testicular feminisation
- Affects 1: 20,000-64,000 male births
- male hormones are normal
- dysfunctional reception to these hormones
CAUSE OF MALE PSEUDOHERMAPHRODITISM
What is leydig cell hypoplasia
- Leydig cells dont secrete testosterone
- Possible due to body insensitisation to LH
- External genitalia normally female/slightly ambiguous
- No female internal genitalia (uterus) develops
CAUSE OF MALE PSEUDOHERMAPHRODITISM
Describe gonadal dysfunction
e.g. XY gonadal dysgenesis aka Swyers Syndrome
- associated wiith XY Karytype
- cause: alteration to Sry gene
- external appearance: female (no menstruation)
- no functional gonads (no testicular differentiation)
- gonad may develop into malignancy
State three examples of tract abnormalities
Uniconuate uterus
Agenesis of the vagina
Ductus deferens: unilateral or bilateral absence
Failure of mesonephric duct to differentiate
Describe gonadal descent
- more apparent and uncommon in males (cryptorchidism) than on females (undescended ovaries)
- Cryptorchidism may be unilateral or bilateral occurring prematurely in 30% of cases. 3-4% may descend in first 2 years
- Undescended ovaries are rare and usually detected in clinical fertility assessment
External genitalia is most common in male hypospadias
Describe an example of abnormal external genitalia
- most common in male hypospadias
- 1:125 live male births
- cause: failure of male urogenital folds to fuse
- outcome: proximally displaced urethral meatus
Is the brain and behaviour implicated in sex and gender?
What is the clinical application of this?
- Sexual behaviour plays a part in gender identity. The brain acquires this independent of influence from androgens but instead from gene expression
- 51 genes identified in mice expressed differently between male and females prior to the advent of androgens. They are active before gonad development
- Potentially help surgeons decide which gender to opt in cases of genital malformation or of transsexualism