1. Introduction to reproductive and sexual differentiation Flashcards
What does bi-potential mean?
The embryo can become male or female
What is sexual determination?
Pathway determining which gender an embryo will become
What is sexual differentiation?
internal and external genitalia being formed (male or female)
What are they different types of sex?
Genotypic, Gonadal, Phenotypic, Legal, Gender Identity
What is genotypic sex?
XX= female XY= male
What is gonadal sex?
What the gonads develop as from the embryonic cells (testes or ovaries)
What is phenotypic sex?
Physical- the parts of the male/female
What is legal sex?
Gender mentioned on passport/birth certificate
decided by midwife
used to be fixed- now can change
important for sports teams
What happens at the genital ridge?
becomes either the testis or the ovaries
Where does the genital ridge develop from?
posterior wall of the lower thoracic lumbar region
What is the genital ridge made of?
common somatic mesenchymal tissue
What does the mullerian duct become?
uterus, uterine tubes and upper 2/3 of vagina
What does the Wollfian duct become?
vas deferens, seminal vesicle and prostate gland
What is the smallest chromosome in a karyotype?
Y chromosome
What does the Y chromosome contain?
SRY gene (sex determining Region of the Y) on the short arm
Where are the SRY genes expressed?
in the sertolli cells
sertolli cells influence the genital ridge to become testes
What does the SRY gene do?
codes for a protein= transcription factor
transcripts itself= develops into male
What are primordial germ cells?
small cluster or cells in the yolk sac= divide mitotically
Where do the primordial germ cells go?
yolk sac to connective tissue of hind gut to developing kidney region to genital ridge
What do the primordial germ cells become?
gametes (sperm/egg)
What are primitive sex chords?
cells near the genital ridge
What do primitive sex chords express in males?
SRY
they become sertoli cells
What do primitive sex chords become in females?
granulosa cells
Where do mesonephric cells originate?
mesonephric primordium = lateral to genital ridges
What do mesonephric cells become in males?
leydig cells= produce testosterone
What do mesonephric cells become in females?
theca cells
What do sertoli cells do?
form tube strucutre around gametes make AMH (anti-mullerian hormone)= involved in further development
What do granulosa cells do?
make oestrodiol in adult life
What do Mesonephric cells form in males?
- make leydig cells
- make vascular tissue
- make basement membrane= forming seminiferous tubules and rete testes
What do Mesonephric cells form in females?
- theca cells
- make vascular tissue
- synthesize androstenedione which is a substrate for estradiol production by the granulosa in adult life
What does anti mullerian hormone do?
regresses mullerian duct (HAPPENS IN MALES)
What are the wollfian ducts stimulated by?
testosterone
What does 5 alpha reductase do?
adds extra H to testosterone= becomes DHT (by converting NADPH to NADP)
What does DHT bind to?
same receptor as testosterone but 10x more potent
What does DHT cause?
produced in males causes external differentiation •the clitoral area enlarges into penis •the labia fuses and becomes ruggated to form a scrotum •a prostate forms
Is 5 alpha reductase present in females?
yes but no tesosterone to make DHT
What does the external genitalia initially look like in males and females?
genital tubercle, genital swelling, urethral fold, urogenital membrane
What happens to the male external genitalia?
- genital tubercle swells = becomes the glans penis
- urethral fold expands = becomes the scrotum
- urethral fold folds over on itself and makes a hollow tube making the shaft of the penis
What happens to the female external genitalia?
- no testosterone= so no DHT
- genital tubercle becomes the clitoris
- urethral fold becomes the labia
What is sex reversal?
phenotype and genotype dont match e.g. female genitalia but Y chromosome
What is intersex?
ambiguous genitalia
What is gonadal dysgenesis?
abnormal gonad development
Who does AIS affect?
males (XY)
What could be cause of AIS?
Testosterone receptor mutation
What will happen in AIS?
- no uterus/ any female internal genitalia= bc AMH so mullerian ducts regress
- no internal male genitalia = wolfian ducts will not develop due to the insensitivity to testosterone
- no convert to DHT so no male external genitalia= so person has external female genitalia
What is partial AIS?
- problem with SOME isoforms of androgen receptors
OR downstream signalling problem - patient has: varying degrees of penile and scrotal development from ambiguous genitalia to large clitoris
What happens with 5 alpha reductase deficiency?
testosterone is made but DHT isnt
What do patients present with when they have 5 alpha reductase deficiency?
no uterus bc AMH is produced
male internal genitalia (only testosterone needed for this)
no male external genitalia (bc no DHT)
PRESENT AS FEMALE
What kind of genetic problem is 5 alpha reductase deficiency?
autosomal recessive
What is turner’s syndrome?
Only 1 X chromosome and no 2nd chromosome
XO
What happens in turner’s syndrome?
- have mullerian ducts bc no Y chromosome so no SRY so no AMH
- have ovary
- no wolfian ducts bc no testosterone
- have female external genitalia as there is no testosterone
What is congenital adrenal hyperplasia?
XX female exposed to high androgen levels in utero
What is the shape of cholestrol?
3x 6 sided rings
1x 5 sided ring and carbon chain sticking out of 5 carbon ring (total 27 carbons)
How are progestogens made?
cleave C 22-27 (SO 21 C IN TOTAL)
How are androgens made?
cleave C 20-27 (19 C IN TOTAL)
In the adrenal glands, how are mineralcorticoids (aldosterone) and glucorticoids (cortisol) made?
progestogens converted to them by 21 hydroxylase
What happens in CAH?
- 21 hydroxylase no function in females
- so then get no aldosterone/cortisol
- so then progestogens go up
- converted to testosterone
- then get wollfian duct to grow
- get male genitalia
What do you present as with CAH?
xx= FEMALE
NO amh AND HIGH TESTOSTERONE- so both male and female internal genitalia
external male genitalia
When does sexual differentiation start?
7 weeks
