Development of the Reproductive System

Question 1

Until what week is the embryo indifferent (no sex)?

Answer 1

week 6

Question 2

When does sexual differentiation begin?

Answer 2

week 7

Question 3

When can female and male genitalia be recognized?

Answer 3

week 12

Question 4

When is phenotypic differentiation complete in the embryo?

Answer 4

week 20

Question 5

What are primordial germ cells?

Answer 5

progenitor cells of oogonia and permatogoonia

Question 6

How do primordial germ cells migrate?

Answer 6

–>specified in epiblast, end up in yolk sac wall after gastrulation and body folding

–>migrate up dorsal mesentery to enter genital ridge of intermediate mesoderm

WEEK 5

Question 7

Describe the location and appearance of primitive gonads during week 6

Answer 7

Initially a pair of longitudinal swelling in urogenital ridges of intermediate mesoderm
–>T10

Question 8

How are primitive gonads formed?

Answer 8

proliferation and delamination of coelomic epithelium

condensation of underlying mesenchyme

Question 9

What stimulates formation of somatic support cells?

Answer 9

primordial germ cells

Question 10

How are somatic support cells formed during week 6?

Answer 10

proliferation and delamination of cells from coelomic epithelium of genital ridge

–> stimulated by primordial germ cells

Question 11

What eventually differentiate into Sertoli cells in males?

Answer 11

somatic support cells

Question 12

What eventually differentiates into follicle cells in females?

Answer 12

somatic support cells

Question 13

What are the 2 sets of reproductive ducts that form within the intermediate mesoderm?

Answer 13

1: mesonephric tubules and duct (wolffian)
2: paramesonpehric duct (Mullerian)

Question 14

What are the fxns of Wolffian/mesonephric ducts?

Answer 14

form within urogenital ridge

–>early collecting ducts for kidney

–>open into urogenital sinus

Question 15

What are the fxns of Mullerian/paramesonephric ducts?

Answer 15

ducts form on both sides from invagination of urogenital ridge

–>cranially, open to coelomic cavity

–>caudally, meet with each other and attach to urogenital sinus

Question 16

What is the key to sexual dimorphism?

Answer 16

Y chromosome

–>contains SRY that codes for testis

*also requires autosomes

Question 17

What occurs in the absence of SRY gene?

Answer 17

formation of female reproductive organs

Question 18

What does SRY turn on to drive male repro formation?

Answer 18

days 42-52

+ SOX9 expression in somatic support cells
—>Sertoli cell diff.

suppresses WNT4
–>pro-female gene

Question 19

What make up testis cords?

Answer 19

-Sertoli cells
surround germ cells
-Primordial germ cells
-Differentiating myoepithelial cells

–>U shaped cords that develop into seminiferous tubules after birth

Question 20

What are the rete testis?

Answer 20

like testis cords but don’t have germ cells

Question 21

How are the testis cords linked to developing epididymis and vas deferens?

Answer 21

Testis cord attaches to rete testes–>connected to efferent ductules (remnant of mesonephric tubules)

Question 22

What are derivatives of the mesonephric duct?

Answer 22

epididymis

vas deferens

Question 23

Primordial germ cells differentiate into _______

Answer 23

type A spermatogonia 3 months after birth, hault until puberty

Question 24

What makes fetal Leydig cells?

Answer 24

subset of intertubular cells differentiate into fetal Leydig cells
–>produce testosterone during week 9-10 to influence genital ducts and external genitalia

Question 25

When do fetal Leydig cells start making testosterone?

Answer 25

weeks 9-10

Question 26

What cells express anti-Mullerian hormone?

Answer 26

Sertoli cells

Question 27

What is the fxn of anti-Mullerian hormone?

Answer 27

drives regression of paramesonephric ducts

Question 28

When are paramesonephric ducts inhibited by anit-mullerian hormone?

Answer 28

weeks 8-10

Question 29

What do remnants of paramesonephric duct make?

Answer 29

- appendix testis | - prostatic utricle

Question 30

What do mesonephric tubules and ducts form?

Answer 30

- Efferent ductules from remaining mesonephric tubules - Epididymis - Vas deferens - Seminal vesicles

Question 31

What drives mesonephric tubule remnants?

Answer 31

Leydig cell-derived testosterone

Question 32

What is the paradidymis?

Answer 32

remnant of lower mesonephric tubules that are NOT used to make efferent ductules

Question 33

What drives development of external genitalia?

Answer 33

DHT via 5a-reductase

Question 34

What does DHT promote formation of?

Answer 34

- penis - scrotum - prostate - ->testicular descent

Question 35

What drives fetal Leydig cells to produce testosterone?

Answer 35

HCG

Question 36

What are the fxns of ADULT Leydig cells?

Answer 36

generate androgens--> spermatogenesis masculinization of brain and male sexual behavior

Question 37

What regulates testosterone production at puberty?

Answer 37

LH

Question 38

What germ layer makes up seminal vesicles?

Answer 38

intermediate mesoderm of urogenital ridge

Question 39

What is formed from buds emanating from the mesonephric duct?

Answer 39

seminal vesicles

Question 40

What forms from buds emanating from endoderm of urogenital sinus (within future region of pelvic urethra)?

Answer 40

prostate gland -->week 10

Question 41

What germ layer makes up prostate gland and bulbourethral glands?

Answer 41

endoderm of urogenital sinus

Question 42

What forms from endoderm buds?

Answer 42

bulbourethral glands

Question 43

What is ectodermal-covered mesodermal swelling at distal end of phallic urogenital plate?

Answer 43

genital tubercle -->growth depends on DHT

Question 44

How is the urogenital plate formed?

Answer 44

Cloacal membrane ruptures, roof of the phallic segment expands along lower surface of genital tubercle as it enlarges -->endodermal extension under genital tubercle

Question 45

What drives lengthening and growth of genital tubercle and fusion of labioscrotal swellings?

Answer 45

DHT

Question 46

How is the tubular penile urethra formed?

Answer 46

urogenital folds fuse midline from perineal to gland penis -->converts urethral groove into penile urethra

Question 47

Where is the urethral groove?

Answer 47

ventral surface of urogenital plate

Question 48

Where are the labioscrotal swellings in relation to urethral folds?

Answer 48

on either side

Question 49

What contains gonadal vessels, N, lymph to testis at T10?

Answer 49

suspensory ligament

Question 50

What connects developing gonad to base of labioscrotal swellings?

Answer 50

gubernaculum -->eventually shortens to pull testes into scrotum

Question 51

Describe hypospadias

Answer 51

most common male birth defect after cryptorchidism -->failure of urethral folds to close properly *urethral opening on underside of penis instead of tip

Question 52

Describe epispadias

Answer 52

d/t improper ventral body closure -->urethra opening on top of penis instead of tip

Question 53

In absence of SRY, somatic support cells express _________

Answer 53

WNT4 and FOXL2

Question 54

What is the fxn of FOXL2?

Answer 54

continually suppresses any SOX9 expression -->maintains female gonad differentiation by continually suppressing Sertoli and Leydig formation

Question 55

What induces somatic support cells to become follicular cells?

Answer 55

developing oocytes

Question 56

What is responsible for arresting primary oocytes in prophase 1 of meiosis until puberty?

Answer 56

surrounding follicle cells

Question 57

Are paramesonpehric ducts retained in males or females?

Answer 57

females

Question 58

What are the remnants from mesonephric ducts in females?

Answer 58

epoophoron and paraoophoron near ovary

Question 59

Describe uterine tube formation

Answer 59

Paramesonephric ducts fused at caudal end by week 9-10 - ->fusion of inferior end forms uterus - ->un-fused portion forms uterine tubes

Question 60

What are uterus anomalies d/t improper fusion of paramesonephric ducts?

Answer 60

1: Didelphys (double uterus) 2: Bicornate uterus (2 bodies, 1 cervix) 3: Double uterus and double vagina 4: Double uterus 5: Unicornate uterus (1 uterine tube) 6: Septated uterus

Question 61

What do the paramesonephric ducts form?

Answer 61

uterine tube uterus vagina

Question 62

What is included in external female genitalia?

Answer 62

labia clitoris lower vagina

Question 63

Describe formation of the vagina

Answer 63

Paramesonephric duct contacts urogenital sinus--> prolif and formation of sinuvaginal bulb sinuvaginal plate lengthens, canalized

Question 64

What germ layer makes up the vagina (except upper fornix)?

Answer 64

endoderm

Question 65

Describe vaginal agenesis

Answer 65

Failure of normal sinuvaginal bulb development or canalization d/t agenesis of paramesonephric ducts

Question 66

What aspects of the phallic segment of urogenital sinus are the same in men and women initially?

Answer 66

urogenital plate glans plate genital tubercle

Question 67

Why is there no lengthening of the genital tubercle or fusion of labioscrotal/urogenital folds in females?

Answer 67

no DHT (via no testosterone)

Question 68

What forms the labia minora?

Answer 68

urogenital folds

Question 69

What forms the labia majora?

Answer 69

labioscrotal folds

Question 70

What separates urethra from vaginal opening?

Answer 70

differential growth and expansion of tissue

Question 71

What ligament is the portion of gubernaculum between the gonad and uterus?

Answer 71

round ligament of ovary

Question 72

What ligament is the portion of gubernaculum between the uterus and base of labioscrotal swellings?

Answer 72

Round ligament of uterus

Question 73

What restricts further ovarian descent?

Answer 73

gubernaculum attachment via round ligaments

Question 74

What is attached to the ovary during its descent?

Answer 74

suspensory ligament superiorly gubernaculum connecting gonad to labioscrotal swelling (majora)

Question 75

What is a double fold of peritoneum (from urogenital ridge) that supports the uterus and ovary?

Answer 75

broad L mesovarian mesosalpinx

Question 76

Describe pathogenesis of 46 XY DSDs

Answer 76

testes but phenotypicallly female - -> inadequate testosterone synthesis (17B deficienty) - ->androgen insensitivity syndrome d/t loss of fxn of androgen receptors - ->5a-reductase deficienty (no DHT) - ->mutations in anti-mullerian hormone

Question 77

Describe mutations in AMH that cause DSDs

Answer 77

retention of paramesonephric ducts-->individuals have uterus and uterine tubes along with male ducts and external genitalia

Question 78

Describe 5a-reductase deficiency in DSDs

Answer 78

AR - normal testis and duct system - underdeveloped external genitalia

Question 79

Describe consequences of androgen insensitivity syndrome

Answer 79

- have testes but no spermatogenesis - @ puberty, testosterone converted to estradiol to + female secondary characteristics - produce AMH so no uterus or tubes but vagina is short and ends blindly - testis found in inguinal or labial regions increases risk of cancer

Question 80

What is the most common cause of 46 XX DSDs

Answer 80

congenital adrenal hypoplasia -->deficiency in 21-hydroxylase-->excess ACTH-->excess androgen production

Question 81

Describe sx of 46 XX DSDs

Answer 81

ovaries female external genitalia masculinized -->can look like hypospadias

Question 82

Describe ovotesticular disorders

Answer 82

- have both testicular and ovarian tissue - ambiguous external genitalia or predominantly female - have uterus **usually karyotype 46XX

Question 83

What are causes of ovotesticular disorders?

Answer 83

1: Translocation of piece of Y chromosome onto X chromosome 2: subset of cells may have mutation in Y chromosome 3: anomaly in sex determination and differentiation of primordial germ cells

Question 84

What is associated with extrophy of the bladder?

Answer 84

epispadias