Lecture 26: Development of the Reproductive System

Question 1

When does the gonadal system start developing?

What germ layer do gonads form from?

Answer 1

Week 5, when the gonads differentiate into male/female specific

Intermediate mesoderm

Question 2

What are the precursor cells for gonads and what happens to them at the start of reproductive development?

Answer 2

Primordial germ cells in epiblasts > migrate to yolk sac during gastrulation > enter genital ridge via dorsal mesentery

Question 3

After migration to the urogenital ridge, what forms?

When does this happen?

Answer 3

PGCs form longitudinal swellings at T10 > induce proliferation in coelemic cells in the nephrogenic cord > form primitive gonadal ridge

Week 6

Question 4

What is the fate of the coelemic cells?

Answer 4

differentiate into support cells (primitive sex chords).. They eventually become Sertoli (male) & follicle (female)

Question 5

What are the two genital ducts and what do they eventually become?

Answer 5

Mesonephric (Wolffian) duct - male tract
Paramesonephric (Mullerian) duct - female tract

*both come form from the urogenital ridge

Question 6

How do the genital ducts develop?

Answer 6

Mesonephric ducts: come from the mesonephric kidney > become collecting duct for the kidney > empty into the urogenital sinus

Paramesonephric ducts: form on aterolateral urogenital ridge > attached to the urinary sinus (caudal) and coelemic cavity (cranial)

Question 7

What is the importance of the Y chromosome in sexual dimorphism/determination?

Answer 7

contains the SRY gene that induces male gonadal (testis) and duct development

w/o it, embryo defaults to female

Question 8

What happens to the Paramesonephric duct in males

When and how does this happen?

Answer 8

degenerates between wk 8 -10

SRY > Sox 9 induction/Wnt 9 suppresion > support cell differentiation into Sertoli > AMH (anti mullerian hormone) > degeneration of the duct

Question 9

What other effects do fetal Sertoli cells have on gonadal development?

Answer 9

they surround inter-tubular cells > release androgen binding factor and form around the seminiferous tubules to house sperm

Question 10

How does the mesonephric duct develop in males?

When does this happen?

Answer 10

Remaining inter-tubular cells > fetal Leydig cells > testosterone > induces differentiation of organs

Week 9 - 10

Question 11

What organs form from the mesonephric duct after induction by testosterone?

What are the remnants of the paramesonephric duct?

Answer 11

-vas deferens, efferent ductules, epididymis, seminal vesicles

appendix epidydymis, prostatic utricle

Question 12

What roles does placental HCG play in male gonadal development?

Answer 12

1.) Week 8-12: induce fetal Leydig cells to Produce testosterone > differentiation of the mesonephric duct

Question 13

How does the penis, scrotum and prostate develop and from which structures do they form?

Answer 13

some of the testosterone produced by fetal Leydig cells is converted to DHT by 5a reductase

forms the genial tubercle (penis), genital swellings (scrotum) and endodermal urethral epithelium (prostate)

Question 14

From which germ layers do seminal vesicles and bulbourethral glands develop from?

Answer 14

• intermediate mesoderm of urogenital ridge

- endoderm

Question 15

What is the initiating event of external genitalia development?

Answer 15

Indifferent external genitalia > cloacal membrane ruptures > phallic portion of the urogenital sinus opens up forming the endodermal urogenital plate

Question 16

What other structures develop from the formation of the urogenital plate?

Answer 16

• Glans plate (on ventral face of urogenital plate)

- Genital tubercle (surrounds the glans plate)

Question 17

After the urogenital plate forms, what structures will develop and how?

Answer 17

Mesoderm proliferates under the covering ectoderm > urogenital/cloacal folds develop on each side of the urogenital plate > labioscrotal swellings form on each side of the cloacal folds

Question 18

After the folds develop, how does the male external genitalia develop? What molecule is responsible for the formation of these structures?

Answer 18

• urogenital folds will fuse to close the opening and the labioscrotal swellings will fuse to form the scrotum
• Genital tubercle elongates forward to form the penis
• Urethral folds fuse at the distal end of the penis
• DHT

Question 19

Hyposopadia

Epispadia

Answer 19

• urethral folds fail to close properly, urethral opening on ventral side rather than distal
• urethra opens on the dorsal side of the penis, associated with exstrophy of the bladder

Question 20

How does the ovary develop?

Answer 20

No SRY > Wnt4 remains and FoxL2 suppresses Sox 9 > maintenance of the female gonad by suppressing Sertoli and Leydig cell differentiation

Question 21

How do oocytes develop?

What are the support cells for oocytes?

Answer 21

Primordial germ cell > oogonia > oocytes

Somatic cells differentiate into follicle cells that surround oocytes and block them to arrest at prophase I

Question 22

If no Sertoli and Leydig cells are formed, what happens differently in female gonadal development?

Answer 22

No sertoli - no AMH > keep the paramesonephric duct

No Leydig > no testosterone > mesonephric duct degenerates

Question 23

How does the uterus develop?

When does this occur?

Answer 23

Paramesonephric ducts fuse inferiorly
Unfused superior parts become uterine tubes

Weeks 9 - 10

Question 24

What is the major cause of uterus and vagina formation anomalies?

Answer 24

Failure of proper fusion of the paramesonephric ducts

Also failure of sinovaginal bulb formation or canalization (for vagina)

Question 25

How does the vagina develop?

What germ layer is it derived from?

Answer 25

Urogenital sinus thickens and forms the sinuvaginal bulb > elongates > canalized to form the opening

Endoderm

Question 26

After the folds develop, how does the female external genitalia (labias and clitoris) develop?

Answer 26

Absence of testosterone and DHT > fusions don’t happen and genital tubercle does not elongate

Urogenital folds - labia minor
Labioscrotal folds - labia major
Genital tubercle - glans clitoris

Question 27

How does the broad ligament, mesovarian and mesosalpinx develop?

Answer 27

• lower urogenital ridge is pulled into the pelvic cavity as paramesonephric ducts fuse midline to form the uterus
• gets covered in peritoneum and thins out

Question 28

How do the round ligaments of the ovary and uterus develop?

Answer 28

Gubernaculum is attached to the developing uterus, so it doesn’t descend as low as the testes do

Superior gubernaculum - round ligament of the ovary
Inferior gubernaculum - round ligament of the uterus

Question 29

46, XY DSDs (Male)
Cause
Clinical

Answer 29

• inadequate testosterone/DHT (17-B hydroxysteroid dehydrogenase or 5a reductase deficiency), androgen insensitivity, AMH or AMH receptor mutations
• phenotypic female with testes

Question 30

Androgen Insensitivity syndrome (Male)
Cause
Clinical

Answer 30

• loss of functional androgen receptors, have high testosterone and AMH (paramesonephric system is suppressed)
• have testis with no spermatogenesis, can develop female characteristics at puberty due to formation of estradiol from testosterone

Question 31

5a reductase deficiency (Male)

Answer 31

• converts Testosterone to DHT

- normal testis and duct system but underdeveloped external genitalia

Question 32

46 XX DSD (Female)
Cause
Clinical

Answer 32

• Congenital adrenal hyperplasia - mutations in adrenocorticosteroid synthesis > excessive androgens
• have ovaries but masculanized external genitalia