Development of the Genital System

Question 1

What is the general timeline for development of the genital system?

Answer 1

Weeks 1-6 = indifferent embryos

Week 7 = sexual differentiation begins

Week 12 = female and male genitalia can be recognized

Week 20 = phenotypic differentiation complete

Question 2

Primordial germ cells within the indifferent gonad are thought to arise from _____ cells that end up in the yolk sac wall after gastrulation and body wall folding. They migrate up the _____ ____ to enter the genital ridge around week ____

Answer 2

Epiblast; dorsal mesentery; 5

[they are NOT of endodermal origin]

Question 3

Around week 6 the primordial germ cells in the indifferent gonad complete their migration to the genital ridge. There are somatic support cells there, which differentiate into _____ cells in males, or ______ cells in females

Answer 3

Sertoli; follicle

Question 4

What are the 2 genital ducts that develop around week 6-7 of development?

Answer 4

Mesonephric ducts (Wolffian)

Paramesonephric ducts (Mullerian)

Question 5

Both mesonephric and paramesonephric ducts form in _____ _____ of the urogenital ridge

Answer 5

Intermediate mesoderm

Question 6

Fate of mesonephric ducts in males vs. females

Answer 6

Males: epididymis, vas deferens, seminal vesicle, ejaculatory duct

Females: degenerates

Question 7

Fate of paramesonephric ducts in males vs. females

Answer 7

Males: degenerates

Females: oviduct, uterus, upper vagina

Question 8

Sexual dimorphism is dependent on the ____ chromosome but also autosomes

The ____ gene is the sex-determining region on the above chromosome, it determines gonad type, which determines duct and genitalia development

Answer 8

Y; SRY

Question 9

In the absence of SRY gene, development is ________. There are also other genes that positively drive this development

Answer 9

Female

Question 10

The SRY gene is also called _______; it is present on the Y chromosome and is active from 41-52 days. It s expressed in _______ cells and upregulates testis specific genes.

Answer 10

TDF (testis determining factor); somatic support (pre-sertoli)

Question 11

______ cells surround primordial germ cells in males to organize seminiferous tubules. A subset of intertubular cells differentiate into ________ cells, which are recruited by the cell type mentioned above

Answer 11

Sertoli; fetal Leydig

Question 12

Sertoli cells express SRY gene, which gives off _______ signal and ________ hormone leading to the regression of _____ ducts between weeks 8-10

Answer 12

Sox9; Anti-Mullerian (aka Mullerian Inhibitory Substance); Mullerian/paramesonephric

Question 13

Although the mullerian ducts regress between weeks 8-10 in males, they leave behind what 2 small tissue remnants?

Answer 13

Appendix testis

Prostatic utricle

Question 14

Leydig-derived testosterone drives the mesonephric tubules and ducts to form what 4 major structures in males?

Answer 14

Efferent ductules
Epididymis
Vas deferens
Seminal vesicles

Question 15

Full degeneration of paramesonephric ducts in males is typically complete by what week of development?

Answer 15

Week 9

Question 16

What 2 hormones are secreted by sertoli cells driving male differentiation?

Answer 16

AMH —> regression of paramesonephric ducts

Androgen binding factor (binds its receptor on sertoli cells at puberty) —> spermatogonia differentiate into spermatozoa

Question 17

There are 2 populations of Leydig cells — fetal and adult. The fetal leydig cells are important for male differentiation. They secrete ______ at weeks 8-12, driven by ____ of the placenta, leading to differentiation of the mesonephric duct into the ductus deferens, epididymis, and seminal vesicles. They also secrete _________, which changes testosterone to DHT

Answer 17

Testosterone; HCG; 5-alpha-reductase

Question 18

DHT is required for:

_________ development into the penis

________ development into the scrotum

_______ development into the prostate

Answer 18

Genital tubercle

Genital swellings

Urethral epithelium

Question 19

What hormones are secreted by adult Leydig cells that encourage male differentiation?

Answer 19

Androgens — lead to initiation of spermatogenesis, masculinization of brain, male sexual behavior

Question 20

When do fetal leydig cells regress?

Answer 20

Fetal or early post-natal life

Question 21

The seminal vesicle buds from the ______ duct, which is composed of _______ of the urogenital ridge

Answer 21

Mesonephric; intermediate mesoderm

Question 22

The prostate gland buds from the ______ of the urogenital sinus in the region of the pelvic urethra; this occurs around week ____

Answer 22

Endoderm; 10

Question 23

The bulbourethral glands also develop as ______ buds

Answer 23

Endodermal

Question 24

The fetus begins with indifferent genitalia, including a ______ ____ which is a remnant of the ruptured cloacal membrane — opening a phallic portion of the urogenital sinus to the exterior, forming an ________-lined plate.

The _______ ____ consists of the remnants of cloacal membrane at the ventral end of the urogenital plate and adjacent ______ ______, which is an ectodermal-covered mesodermal swelling at the ventral and cranial ends of phallic portion of the urogenital plate

Answer 24

Urogenital plate; endodermally

Glans plate; genital tubercle

Question 25

The genital tubercle is an _______-covered ________ swelling at the ventral and cranial end of phallic portion of urogenital plate

Answer 25

Ectodermal; mesodermal

Question 26

The tip of the urorectal septum seen at the exterior is known as the __________

Answer 26

Perineal body

Question 27

The testis start up around ______, and are attached and pulled inferiorly by the _______, eventually anchoring them in the scrotum

Answer 27

T10; gubernaculum

Question 28

What is the most common urethral birth defect in males after cryptorchidism?

Answer 28

Hypospadias

Question 29

Epispadias is associated with what other GU birth defect?

Answer 29

Exstrophy of the bladder

Question 30

In the absence of SRY, development is female. What are 2 other major pro-female genes?

Answer 30

Wnt-4 — initially suppresses SOX-9 expression FOXL2 — continually suppresses SOX-9, maintaining female gonad (suppresses Sertoli and Leydig differentiation)

Question 31

In females, somatic cells differentiate into ____ cells and primordial germ cells differentiate into _____, which later differentiate into ____

Answer 31

Follicle; oogonia; oocytes

Question 32

______ cells surround oocytes. Since there are no Sertoli cells, no ____ hormone is secreted so the _____ ducts are retained. There are also no Leydig cells, so the _____ duct system is lost

Answer 32

Follicle; AMH; paramesonephric; mesonephric

Question 33

The uterus forms around week ____-____ from fusion of inferior _______ ______

Answer 33

9-10; paramesonephric ducts

Question 34

The unfused superior portion of the paramesonephric ducts forms the ______ in females

Answer 34

Oviducts

Question 35

_______ = double uterus

Answer 35

Didelphys [due to absence of fusion of inferior paramesonephric ducts during development — leading ot double uterus, double vagina, bicornate uterus, septated uterus, unicornate uterus, cervical atresia, etc.]

Question 36

The vaginal plate is eventually canalized during development. The upper vagina is derived from _____, while the lower vagina is derived from _____

Answer 36

Mesoderm; endoderm

Question 37

________ = condition characterized by failure of normal vaginal plate development or failed canalization

Answer 37

Vaginal agenesis

Question 38

Female external genitalia development starts out the same as in males, with the phallic segment of the urogenital sinus forming the urogenital plate, glans plate, and genital tubercle. What happens to these structures in the absence of testosterone or DHT?

Answer 38

No lengthening of genital tubercle occurs; no fusion of labioscrotal swellings Labioscrotal swellings —-> labia majora Urogenital folds —> labia minora