ICL 18.1: Embryology of the Male and Female Reproductive System

Question 1

what embryological structure is the genital system derived from?

Answer 1

a common ridge of intermediate mesoderm that lies along the posterior abdominal wall

this is the same for the urinary system which comes from the same embryological structure!!

Question 2

when do the male and female genital systems differentiate during development?

Answer 2

up until the end of the 6th post conceptional week, the reproductive system is indifferent, i.e., no male/female distinction

the embryo is undifferentiated until the beginning of the 7th week

gonadal differentiation (ovaries vs. testes) determines how reproductive tract and external genitalia develop

Question 3

what are the structures that are part of the intermediate mesoderm during development?

Answer 3

urogenital ridge has 2 parts:
1. genital ridge

2. nephrogenic cord

has 2 ducts that are critical for male/female reproductive organs = mesonephric duct and paramesonephric duct

Question 4

where do the gonadal cells originate from?

Answer 4

the GI system develops from the endoderm

the gametes don’t start in the gonads! the primordial germ cells migrate from the yolk sac in the endoderm along the dorsal mesentery of the GI tract to the genital ridge of the mesoderm

Question 5

where do the gonads come from?

Answer 5

the gonads are derived from the genital ridge (intermediate mesoderm)

primordial germ cells (precursors to the gonads) migrate from the yolk sac to the genital ridge and land in the outer epithelial layer of the genital ridge

at this time (6 weeks post conception), the gonad is undifferentiated and at this time you start to functionally differentiate into testes vs. ovaries!

at this point you have epithelial projections into the mesoderm with the developing gonads which are your primary sex cords! you primary sex cords are part of the proliferating epithelium of the genital ridge that contain the primordial germ cells

Question 6

how do the gonad know to become testis?

Answer 6

if a Y chromosome is present, the SYR gene on this chromosome codes for testes determining factor (TDF)

TDF results in some of the primary sex cord cells being transformed the tubules of the testis and into Sertoli cells which will produce muellerian inhibiting substance (MIS)

MIS stimulates interstitial (Leydig) cells to produce testosterone

primitive sex cords contain primordial germ cells which have differentiated into spermatogonia that are supported by Sertoli and Leydig cells which product MIS and testosterone which are critical for the development of the rest of the male reproductive tract

Question 7

how do the gonad know to become ovaries?

Answer 7

if there’s no TDF present, you develop an ovary

the primary sex cords degenerate and become an embryonic remnant and you get a secondary proliferation of the epithelial covering called your secondary sex cords which contain your primordial germ cells

as the secondary sex cords proliferate they will proliferate in follicular-like structures –> so the primordial germ cells called oogonia are surrounded by the secondary sex cells

Question 8

what do the primitive sex cords become if you are destined to be a boy?

Answer 8

medullary cords

1. seminiferous tubules (PGCs –> spermatogonia)
2. straight tubules
3. Rete testis

Question 9

what are sertoli cell and what are they derived from?

Answer 9

derived from seminiferous tubules of the primitive sec cords

they surround primordial germ cells and secrete MIS

Question 10

what are Leydig cells?

Answer 10

they’re in-between the sertoli cells

secrete testosterone

Question 11

what do the primitive sex cords become if you are destined to be a girl?

Answer 11

primitive sex cords degenerate!

secondary sex cords develop and they become primordial follicles that contain premordial germ cells that become oogonium

Question 12

which embryologic structures gives rise to a primordial follicle?

Answer 12

secondary sex cord

Question 13

what is the origin of the internal reproductive tracts?

Answer 13

nephrogenic ridge:

paramesopnephric ducts –> female reproductive tract (uterus, fallopian tubes, cervix, part of vagina)

mesonephric ducts –> male reproductive tract (vas defers, seminal vesicle)

cloaca (distal part of hindgut) has the urogenital sinus which becomes the external genitalia

Question 14

if you’re a girl, what happens to the mesonephric ducts?

Answer 14

they will degenerate

your paramesonephric ducts will persist

distally they are fused at the midline which is called the uretovaginal primordial which is critical is forming the internal reproductive tract –> it forms the uterus, cervix and upper vagina

above this fusion, the fallopian tubes form

Question 15

if you’re a girl, what happens to the mesonephric ducts?

Answer 15

they persist and the paramesoneprhic ducts degenerate due to MIS being secreted by the sertoli cells!

the mesonephric ducts then need testosterone to differentiate into the structures of the male reproductive structures:
1. efferent ductules

2. ductus epididymus
3. ductus deferens
4. seminal gland
5. ejaculatory duct

Question 16

where does the lower part of the vagina come from?

Answer 16

the fused part of the paramesonephric ducts (uterovaginoprimordium) connects with the urogenital sinus and becomes the sinovaginal bulb which gives rise to the lower part of the vagina

the sinovaginal bulbs fuse in the midline to form the vaginal plate –> the central cells of the vaginal plate then breakdown to form the lumen of the lower vagina

the upper part comes from the fused paramesonephric duct

Question 17

when does external genitalia start to differentiate?

Answer 17

up until week 7, the external genitalia are similar in both sexes

differentiation of external genitalia begins at week 9

full differentiation occurs by week 12

Question 18

what is the indifferent stage? what are the parts of the undifferentiated genitalia?

Answer 18

when the external genitalia aren’t differentiated

before week 9 you will have:

1. genital tubercle which is the precursor for the phallus (penis or clitorus)
2. cloacal membrane
3. urogenital fold on both sides of the cloacal membrane
4. labioscrotal swelling

Question 19

how does external genitalia turn into male external genitalia? which hormones are responsible for which structures?

Answer 19

testosterone produced by Lydig cells is essential!

testosterone is converted into dihydrotesterone by 5-alpha-reductase

dihydrotesterone presence leads to development of:

1. urethra
2. penis
3. scrotum
4. prostate

testosterone leads to development of:

1. epididymis
2. vas deference
3. seminal vesicles

phallus/genital tubercle –> penis

urogenital folds fuse along ventral surface to form the spongy (penile) urethra

labioscrotal folds fusion –> scrotum

Question 20

how does external genitalia turn into female external genitalia? which hormones are responsible for which structures?

Answer 20

if there isn’t TDF present:

1. phallus ceases to grow and becomes the clitoris
2. unfused urogenital folds form the labia minoria
3. most of the labioscrotal folds remain unfused and form the labia majora

Question 21

how can a phenotypic female be 46, XY?

Answer 21

the main cause is Androgen Insensitivity Syndrome (AIS)

1. this is usually caused by mutations of the gene encoding the androgen receptor AR gene located on the X chromosome or mutation in the SRY gene –> so even though you’re XY, you will undifferentiated gonads with features of both the testis and ovaries – they might have some paramesanephric duct structures and external genitalia will be female but they won’t have menstrual periods because they don’t have ovaries
2. 5-alpha-reductase deficiency = you have testosterone but no dihydrotestosterone –> no male external genitalia but they have testosterone so you will have a vas deferens! and the mesonephric duct persists

rare mutations in key sex determining genes including deletion or mutations of SRY

things that could cause female XY:
1. Y chromosome that direct the gonad to become a testis but there isn’t enough testosterone from the lydig

2. deletion of the SRY gene
3. 5-alpha-reductase deficiency

Question 22

how do gonads move from the abdomen to the pelvis in a male?

Answer 22

gubernaculum anchors the gonad to the labioscrotal folds

depending on whether you’re XX or XY will determine where the gonads end up

if you have testis, the gubernaculum shortens and drags the testis through the abdominal wall and the testis to end up the scrotum and then the gubernaculum anchors the testis to the scrotum –> as the testis go through the abdominal wall is the process vaginalis

Question 23

how do gonads move from the abdomen to the pelvis in a female?

Answer 23

gubernaculum anchors the gonad to the labioscrotal folds

depending on whether you’re XX or XY will determine where the gonads end up

if you have ovarie s, the gubernaculum differentiates into the uterovarian ligament and the round ligament:

1. uterovarian ligament formed by the cranial part of the gubernaculum anchors the ovary to the top of the uterus
2. round ligament formed by the caudal portion anchors the lateral aspect of the uterus to the labia majora

so the ovaries dont have a true descent like the testis but rather a change in position –> ovaries move from posterior abdominal wall to the pelvic brim