L11 - Sexual differentiation - how to make a boy or a girl Flashcards
3 main events determining what makes a boy/girl
1) Sex determination, during fertilisation
2) Differentiation of gonads, week 5
3) Differentiation of internal and external genital organs, after week 5
Which week do primordial germ cells (PGCs) arise from the epiblast
- Week 2
Are PGCs pluripotent or totipotent
- PGCs are pluripotent
Where do PGCs migrate to
- PGCs migrate to yolk sac stalk to avoid becoming imprinted
- Later return, travelling to the genital ridge(next to kidney) and become the indifferent gonad
Where do XX PGCs and XY PGCs replicate
At genital ridge:
- XX PGCs replicate at cortex; XY PGCs replicate at the medulla
What does gonad gender decision rely on
- Genetic switches
- Hormones
Examples of genetic switches
- General transcription factors (eg Wt1, Sf1)
- Specific promoters of testis development (eg Sry, Sox9)
- Specific promoters of ovarian development (Wnt-4, FoxL2)
Fate of gonad cell lines
Urogenital ridge –> Bipotential gonad (Supporting cell precursors, primordial germ cells, steroidogenic precursors ) –> Future ovary (Follicular cells, oocytes, internal theca cells) + Future testis (leydig cells, pro-spermatogonia, sertoli cells)
What do female PGCs differentiate into
- Oogonia (primary oocytes)
What do sex cord cells differentiate into
- Granulosa (support and nutrifying the ovum)
What does the cortex differentiate into
Cortex –> layer of thecal cells –> secrete androgens before those generated by the follicles
What do male PGCs develop into
- Spermatogonia
What causes secretion of AMH(anti-mullerian hormone)
- Sry(Sex-determining region Y) influences definition + identity of sertoli cells –> secretion of AMH
Effects of AMH
- AMH suppresses female development pathway
- AMH induce cells in intermediate mesoderm to become leydig –> secrete testosterone
Origin of kidneys
- Intermediate medosderm between the somites and lateral plate (each side of the aorta)
Stages of kidney development
- Pronephros - disappears soon after
- Mesonephros - leaves remnants (leaves behind ducts that become integral part of the reproductive system)
- Metanephros - becomes kidney
When do internal genital organs begin differentiation
- Week 8, formed from a priori identical primordium structures i.e embryos of both sexes possess two sets of paired ducts at the start
In which gender is the mullerian duct kept
- in female embryo, mullerian duct is kept due to the absence of AMH
What does the mullerian duct give rise to
- Oviduct
- Uterus
- Cervix
- Upper part of the vagina
Effect of AMH and testosterone in the male embryo
- AMH causes mullerian duct regression
- Testosterone promotes wolffian duct differentiation
What does the wolffian duct differentiate into
- Epididymis
- Vas deferens
- Seminal vesicle
What is the genital tubercle
- Elevated midline swelling that occurs during embryo development
What does the genital tubercle consist of
- Urethral groove (opening into the urogenital sinus)
- Paired urethral folds
- Paired labioscrotal swellings
What is some testosterone converted into in males
- Some testosterone is converted into dihydrotestosterone (DHT)
Effect of DHT
- DHT stimulates development of the urethra, prostate and external genitals (scrotum and penis)
What does the genital tubercle eventually develop into
- Penis
What do the paired urethral folds form
- Fusion of the urethral folds –> spongy urethra
What do the labioscrotal swellings form
- Labioscrotal swellings –> scrotum
Is there DHT in females
- DHT is absent
What does the genital tubercle develop into in females
- Genital tubercle –> clitoris
What do the urethral folds form in females
Urethral folds remain open –> labia minora
What do labioscrotal swellings form in females
Labioscrotal swellings –> labia majora
What does the urethral groove form in females
Urethral groove –> vestibule
What is monosomy
- The condition of having a diploid chromosome complement in which one chromosome lacks its homologous partner
Genetic features of turner’s syndrome
- Monosomy, XO
Prevalence of turner’s syndrome
1:2500 females (does not affect males)
Turner’s syndrome - survival rate
- 99% non-viable embryos
- Survivors fail to sexually mature at puberty
- Exhibit several physical abnormalities
What is diagnosis of turner’s syndrome confirmed through
- Diagnosis confirmed through amniocentesis
What is klinefelter’s syndrome
- Klinefelter syndrome (KS) also known as 47,XXY or XXY, is the set of symptoms that result from two or more X chromosomes in males
Prevalence of klinefelter’s syndrome
- 1:600-1000 male births (does not affect females)
- Birth appear normal (undetected)
Effects of klinefelter’s syndrome
- Become infertile
- Exhibit some features associated with female development (eg gynecomastia)
What is diagnosis of klinefelter’s syndrom confirmed through
- Amniocentesis
What are hermaphrodites
- a hermaphrodite is an organism that has complete or partial reproductive organs and produces gametes normally associated with both male and female sexes
Features of true hermaphrodites
- Extremely rare
- Born with both ovarian and testicular tissue (ovotestis)
- 46XX (SRY+), 45X (SRY+) and 45X
Features of female pseudohermaphrodites
- 46, XX with virilization (due to androgens)
- Internal sex organs are normal, including ovaries
- External appearance and genitals - male
- Fusion of labia, enlarged clitoris
Possible cause - true hermaphrodites
- Two ova fertilised by two sperm that fuse to form a tetragametic chimera
Possible cause - female pseudohermaphrodites
- Exposure to male hormones prior to birth(eg. from congenital virilizing adrenal hyperplasia)
Features of male pseudohermaphrodites
- 46, XY
- External genitals - incompletely formed, ambiguous or clearly female
- Blind-ending vagina, absence of breast development, primary amenorrhea
- Testis - normal, malformed or absent
Main causes - male pseudohermaphrodites
- Defective androgen synthesis
- Defective androgen action (eg receptor disorder)
Features of androgen insensitivity syndrome (AIS)
- AKA testicular feminization
- Affects 1:20000-64000 male births
- (Male) hormones are normal
- Dysfunctional receptor to these hormones
What is leydig cell hypoplasia
- Leydig cells do not secrete testosterone
Possible reason for leydig cell hypoplasia
- Body insensitive to LH
Features of leydig cell hypoplasia
- External genitalia normally female/slightly ambiguous
- No female internal genitalia (uterus) develops
What is gonadal dysfunction associated with
- Associated with XY karyotype
Cause of gonadal dysfunction
- Alteration to Sry gene
Features of gonadal dysfunction
- External appearance: female (no menstruation)
- No functional gonads (no testicular differentiation)
- Gonad may develop into malignancy
Examples of tract abnormalities
- Uterine (eg unicornuate uterus)
- Vagina (eg agenesis)
- Ductus deferns (unilateral or bilateral absence, failure of mesonephric duct to differentiate)
What is cryptoarchidism
- The absence of one or both testes from the scrotum
Are problems with gonadal descent more prevalent in males or females
- More apparent and common in males than in females
Features of cryptoarchidism
- May be unilateral/bilateral
- Occurs 30% premature; 3-4% term males
- Descent may take place during year 1
Features of undescended ovaries
- Quite rare
- Detected in clinical fertility assessment
What is hypospadia
Hypospadias is a congenital disorder of the urethra where the urinary opening is not at the usual location on the head of the penis
Prevalence of male hypospadias
1:125 live male births
Features of male hypospadias
- Failure of male urogenital folds to fuse
- Outcome - proximally displaced urethral meatus
What does research suggest about where the brain acquires its gender identity from
- Research from mutants revealed that the brain acquires its gender identity not from the influence of sex hormones but instead from gene expression, given the correlation between inactivation of genes from the X chromosome and predisposition to transexualism
