Abnormal Development of the Reproductive System

Question 1

What triggers testis development?

Answer 1

SRY

Question 2

What secretes AMH?

Answer 2

Testes

Question 3

What causes involution of the Mullerian duct?

Answer 3

AMH

Question 4

What causes differentiation of the Wolffian duct?

Answer 4

Testosterone

Question 5

What does the Wolffian duct form?

Answer 5

Seminal vesicles, epididymis, and vas deferens

Question 6

What 3 things does DHT trigger?

Answer 6

• Genital tubercle → penis
• Labioscrotal folds → scrotum
• Urogenital folds → penile urethra

Question 7

What triggers ovary development?

Answer 7

FOXL2 gene + absence of SRY

Question 8

What triggers differentiation of Mullerian duct?

Answer 8

Absence of AMH

Question 9

What 3 things does the Mullerian duct form?

Answer 9

Fallopian tube, uterus, and upper vagina

Question 10

What causes involution of the Wolffian duct?

Answer 10

Absence of testosterone

Question 11

What causes formation of female external genitalia?

What 4 things form from which precursors?

Answer 11

• Absence of DHT
• Genital tubercle → clitoris
• Folds of urogenital sinus → labia minora
• Labioscrotal folds → labia majora
• Urogenital sinus → urethra and lower vagina

Question 12

What 2 genes are involved in Kallman Syndrome?

Answer 12

KAL 1 / 2

Question 13

4 effects of gonadal dysgenesis

Answer 13

• Low estradiol → high FSH due to loss of neg feedback
• Primary amenorrhea
• Short stature
• If Y chromosome is present, do gonadectomy due to risk of gonadal tumors

Question 14

Mullerian Agenesis (Mayer-Rokitansky-Kuster-Hauser Syndrome)
Karyotype
Presentation

Answer 14

• 46, XX
• Presents as normal female phenotype w/ absence of uterus, upper vagina, and fallopian tubes.
• Ovaries and lower vagina are still present.
• Development is normal except for lack of menses.

Question 15

Imperforate hymen / Transverse vaginal septum
Presentation
Treatment

Answer 15

• Presents w/ hematocolpos and monthly cyclic pain b/c menses can’t drain out. Uterus / upper vagina become distended w/ blood (hematocolpos). May get endometriosis.
• Ovaries are present and development is normal.
• Treat w/ surgery to open up the vagina.

Question 16

Androgen insensitivity in a fetus
Karyotype
Phenotype

Answer 16

• 46, XY karyotype w/ normal (undescended) testes
• But, lack of sensitivity to androgens → female phenotype
• No testosterone receptor → absence male internal genitalia (no Wolffian duct)
• Normal AMH → absent female internal genitalia
• No DHT receptor → absent male external genitalia and presence of female external genitalia (blind vaginal pouch [lower vagina])
• Overall, you get female external genitalia + undescended testes.

Question 17

Androgen insensitivity during puberty
Karyotype
Presentation
Treatment

Answer 17

• 46, XY karyotype w/ normal (undescended) testes
• Testosterone and DHT rise during puberty, but b/c the receptors don’t work:
• No virilization or pubic hair (abnormal androgen receptor)
• Normal breast development (due to peripheral conversion of testosterone to estrogen + normal estrogen receptor)
• Amenorrhea (no uterus due to AMH)
• Overall, get breasts but no period or pubic hair
• Legally and socially female. Testes are removed after puberty due to risk of tumor development.

Question 18

2 syndromes that cause blind vagina

What is the difference?

Answer 18

• Androgen insensitivity syndrome and mullerian agenesis.

* Main diff is that AIS is 46 XY and Mullerian agenesis is 46 XX

Question 19

Classic CAH
Presentation in girls vs boys
2 variants

Answer 19

• Girls present w/ ambiguous external genitalia. Have ovaries and uterus.
• Boys present w/ adrenal crisis (prevent w/ newborn screen).
• 2 variants, both of which present w/ virilization in girls
• Salt wasting – more common. Impaired cortisol and aldosterone → hyponatremia, dehydration, hyperkalemia, hypotension, and shock. Presents w/ early adrenal crisis in both genders.
• Simple virilizing – adequate aldosterone function (only requires 1% of enzyme function). Both genders can have adrenal crisis. Girls have clitoral enlargement and labial fusion. Presentation is less obvious in newborn boys, but later presents w/ very early pubertal signs and risk of adrenal crisis w/ stress.

Question 20

Treating CAH (2)

Answer 20

• Glucocorticoids for adrenal insufficiency. Also reduces androgen levels allowing for ovulation and conception in women.
• Surgery for women to fix ambiguous genitalia