Embryology and CAH Flashcards
True or false: Richardson syndrome is 45, YO.
False. 45, YO is lethal.
Presence of __________ determines male development, regardless of number of X chromosomes.
SRY (the Sex-determining Region of Y)
How does SRY determine male sexual development?
It is a transcription factor that activates a cascade of genes that determines male development.
What is WT1?
Wilms Tumor-related gene
The genital ridges form just medial to the proliferating ________________.
mesonephros
WT-1 deletions and mutations are associated with _________________.
gonadal dysgenesis and Wilms tumors
NR5A-1 is also called __________.
Steroidogenic Factor-1 (SF-1)
SF-1 regulates development of ________________.
the adrenal glands and genes involved in gonadal development
SF-1 deletions result in gonadal dysgenesis and ____________.
adrenal failure
Germ cells migrate from the ____________.
yolk sac
The primitive sex cords development into the ____________.
Sertoli cells
One of the most important transcription targets of SRY is _______________.
SOX-9; mutations in this result in gonadal dysgenesis and skeletal dysplasia (due, in part, to lowered levels of anti-Müllerian hormone)
The urogenital ridge develops into the ________________.
bipotential gonad
Duplication of the DAX gene results in ________________.
dysgenesis of the testes; this is normal in females, but if a male has a DAX duplication, then he will develop small testes
(“It AXes the testes.”)
Which genes stimulate ovarian development?
Wnt/RSPO1 -> beta-catenin
FOXL2
DAX1
In females, what happens to the medullary sex cords?
They degenerate. The cortex becomes the cords.
AMH is secreted by ____________; this must occur by the 8th week.
Sertoli cells
What two hormones are needed for proper development of the internal ducts in males?
AMH and testosterone
What two hormones are needed for proper development of the internal ducts in females?
Trick question –females need absence of AMH and testosterone to develop properly
The paramesonephric ducts development into _____________.
fallopian tubes, uterus, and the upper portion of the vagina
In ________________ syndrome, women have absent Müllerian structures.
Rokitansky (46, XX)
What two molecular abnormalities can lead to persistent Müllerian structures in 46, XY males?
Defects in the AMH receptor or AMH synthesis
The ____________ develops into the glans penis in males and the clitoris in females.
genital tubercle
What structure becomes the labia majora in females and scrotum in males?
The labioscrotal swellings
The urethral folds develop into __________ in females and ____________ in males.
labia minora; penile urethra
In males, the Müllerian duct develops into the _______________.
prostatic utricle
What is the main determining factor in the development of the external genitalia?
Testosterone
Development of the male external genitalia is complete by _____________, so the addition of androgens after that time – in a male who was deficient earlier –will not correct the abnormality.
13 weeks
What occurs to females exposed to excess androgens before and after 13 weeks’ gestation?
Prior: insertion of urethra into vagina
After: clitoromegaly
What would palpable gonads in the labial folds indicate?
Testes (and likely an XY baby)
The two broad categories of disorders of sexual development (DSD) are _____________________.
- 46, XX (virilized)
- 46, XY (undervirilized)
95% of 46, XX DSD is _________________.
congenital adrenal hyperplasia
Underexpression of SOX9 will lead to _________________.
gonadal dysgenesis in a male
Testicular regression is most often due to _________________.
vascular insults in utero
In those with 5-alpha reductase deficiency, the testes are usually in ______________.
inguinal canal or labioscrotal folds
Those with ______________ lack a uterus and have a feminizing puberty.
congenital androgen insufficiency (46, XY)
Bilateral hernia repairs (due to testes) is a symptom of ______________.
CAIS
Why will girls with CAIS develop breasts at puberty?
Because they still have testosterone –it’s just not binding to androgen receptors –and the testosterone gets converted to estrogen.
True or false: 21-alpha hydroxylase deficiency is almost always fatal in the first few months of life if undetected.
False. There are actually milder forms that present in adolescence.
How does 21-alpha hydroxylase deficiency present in males?
Hyponatremia and hyperkalemia with hypotension (the virilziing effects are not of consequence)
StAR syndrome results in what phenotype?
All female, regardless of chromosomal status (because no androgens are produced); it is also called lipoid adrenal hyperplasia, because cholesterol accumulates in the adrenal gland yet cannot be converted to any of its usual derivatives
If yolk sac cells fail to migrate, then _____________ develops.
streak gonads
When does yolk sac cell migration occur?
6 weeks’ gestation
Until when are the gonads undifferentiated?
7 weeks’ gestation (when SRY begins to differentiate in the male)
You know that hCG stimulates Leydig cells. Why is this important?
Males need testosterone to develop, but they don’t start making LH until the second trimester. As such, maternal hCG needs to stimulate LH receptors in the first trimester.
Without _____________, the Wolffian structures regress.
high local concentrations of testosterone
What needs to occur (and when) for the labial folds to fuse?
Exposure to excess androgens prior to 12 weeks’ gestation
How does androgen insensitivity present?
With no uterus or ovaries because the male XY chromosomes produce AMH, but external female genitalia because androgens are needed for male genitalia development. Also, testosterone is needed for maturation of the Wolffian duct structures so male gonads are present intra-abdominally but without the epididymis.
ACTH regulates which enzyme?
20,22-desmolase
True or false: 21-hydroxylase deficiency presents with normal internal sex organs in an XX child.
True! XX females will lack SRY and thus lack testes and AMH and thus normal ovaries and uterus will develop.
An elevated _____________ is diagnostic of CAH.
17-hydroxy progesterone
Which two genes elevate AMH levels?
SF-1 and SOX9
Which cells secrete AMH?
Sertoli cells
At birth, what are normal stretched penile and clitoral lengths?
Penile: greater than 2.5 cm
Clitoris: less than 1.0 cm
