15. Development of Reproductive System

Question 1

When do the indifferent gonad first show up

Answer 1

Week 5

End up in yolk sac wall after gastrulation and body folding

Question 2

Where does the primitive gonadal ridge develop

Answer 2

T10 near primitive mesonephric kidney

Question 3

What structures are derived from the Mesonephric duct (Wolffian)

Answer 3

Epididymis
Vas deferens
Seminal vesicle
Ejaculatory duct

Question 4

What structures are derived from the Paramesonephric duct (Mullerian)

Answer 4

Oviduct
Uterus
Upper vagina

Question 5

What does the SRY gene do

Answer 5

Promote male development and differentiation

• activate SOX9 to activate Anti-Mullerian Hormone (AMH)
• Mullerian ducts regress in weeks 8-10 in presence of AMH

Question 6

When do Leydig cells begin releasing/making testosterone

Answer 6

week 8

Question 7

What are the origins of the seminal vesicle, prostate gland and bulbourethral glands

Answer 7

Seminal- buds from mesonephric duct
Prostate- buds from endoderm of urogenital sinus in region of pelvic urethra (week 10)
Bulbourethral- from endodermal buds

Question 8

What is the genital tubercle in terms of male external genitalia

Answer 8

Ectodermal-covered mesodermal swelling responsible for the phallic portion of the urogenital plate
-DHT drives the lengthening and also fusion of labioscrotal swellings to form scrotum

Question 9

What are hypospadia and Epispadia

Answer 9

Hypospadia- caused by failure of urethra folds to close properly leading to urethral opening on ventral side
Epispadia- urethra opens on dorsal side of penis (associated with exstrophy of bladder)

Question 10

Female genitalia develops in absence of SRY and the presence of a pro-female gene

Answer 10

WNT-4

Question 11

What is the function of FOXL2 in female differentiation

Answer 11

FOXL2 continually suppresses SOX-9 which maintains female gonads

• no sertoli cells means no AMH (persistence of Mullerian duct)
• no leydig cells means loss of wolffian duct

Question 12

How does the uterus form

Answer 12

Fusion of Paramesonephric ducts around weeks 9-10

-Uterine tubes are unfused superior portions of the paramesonephric ducts

Question 13

What is didelphys

Answer 13

Double uterus

Question 14

What is responsible for vaginal formation

Answer 14

Lengthening of sinuvaginal bulb (endodermally derived)

-bulb is eventually canalized

Question 15

In female external genitalia development what happens in the absence of DHT

Answer 15

• no lengthening of genital tubercle

- no fusion of urogenital folds or labioscrotal swellings

Question 16

How is the broad ligament formed

Answer 16

-Upon completion of uterus and oviduct formation, the remaining tissue thins forming a double fold of peritoneum (broad ligament) supporting the uterus and ovary

Question 17

In the female what do the superior and inferior gubernaculum become

Answer 17

Superior- round ligament of ovary

Inferior- round ligament of uterus

Question 18

What can cause a male XY genotype to have testis but the phenotype is female
(MALE DSD)

Answer 18

• Inadequate testosterone synthesis
• Androgen insensitivity syndrome
• 5a-reductse deficiency
• Mutations in AMH or AMH receptor

Question 19

What is Androgen Insensitivity Sydrome

Answer 19

loss of function androgen receptor

• have testes but no spermatogenesis
• produce AMH so paramesonephric system is suppressed, absence of uteres or uterine tubes and vagina is short and ends blindly

Question 20

What is 5a-reductase Deficiency

Answer 20

• Normal testis and duct system develop as there is AMH and tesosterone
• Underdeveloped male external genitalia dependent on DHT

Question 21

What is congenital adrenal hyperplasia

Answer 21

-Most common cause of female sexual ambiguity due to mutations in genes involved in adrenocortical steroid biosynthesis (21-hydroxylase)

Question 22

What is an Ovotesticular disorder

Answer 22

-Have both testicular and ovarian tissue and ambiguous external genitalia
Causes:
-Translocation of piece of Y chromosome onto X chromosome
Subset of cells may have mutation in Y chromosome
-Anomaly in sex determination/differentiation of primary germ cells