Summary: Wk 5: primordial germ cells (from yolk sac) migrate
into singular, undifferentiated gonad (located at T10) Wk 6:
undifferentiated genitalia in males, the medulla attaches to the
mesonephric ducts TESTES In females, the cortex attaches to the
paramesonephric ducts OVARY In both sexes, the cloaca septates into
the bladder and rectum The metanephros (future kidney) buds from
the mesonephric duct Wk 7: both Mullerian and Wolffian ducts are
present Wk 10: Recognizable genitalia
Slide 3
Intermediate Mesoderm Becomes the suprarenal glands, gonads,
kidneys and associated tubes and vasculature
Slide 4
Overview- Male The male reproductive tract forms from Wolffian
ducts Seminal Vesicles Epidydimis Ejaculatory Duct Ductus Deferens
Both the gonads and the Wolffian ducts form from intermediate
mesoderm The Wolffian duct forms from the mesonephric duct(from
intermediate mesoderm), left over from the mesonephros (at wk 12).
Intermediate mesoderm also forms the gubernaculum, which pulls the
testes down into the scrotum
Slide 5
Overview: Male II At wk 5, the gonads receive primordial germ
cells from the yolk sac At wk 6, the medulla of the
undifferentiated gonad attaches to the mesonephric ducts above the
metanephros and becomes the testes. This is induced by
testosterone, stimulated by the SRY gene on the Y chromosome.
Stimulates Sertoli cells to secrete Mullerian inhibiting factor
Stimulates the growth of the Wolffian ducts By week 7, both
mullerian and Wolffian ducts are still present, but testosterone
and MIF are actively produced Descent of the testes is stalled at
the inguinal ring until close to delivery time
Slide 6
Overview: Male III DHT (produced via 5-alpha reductase) induces
external male genitalia differentiation (penis, scrotum) SRY, Sox9
(gonads), AMH/MIF(ducts) gene expression 5-alpha reductase
deficiency: lack of DHT prevents male differentiation until puberty
(female external genitalia changes to penis at puberty)
Slide 7
Overview: Male 2 nd Sex Char. Testicular Androgens External
genitalia development Facial hair Axillary and pubic hair
Enlargement of laryngeal cartilageand deepening of the voice
Increased muscle mass GH (adenohypophysis) Broadening of shoulders
Increased muscle mass Estrogen Growth spurt: estrogen receptors in
bone
Slide 8
Overview-Female The female reproductive tract forms from the
Mullerian duct and the gonads, which are both formed from
intermediate mesoderm The Mullerian duct does NOT form from the
mesonephric duct, rather it forms from the paramesonephric ducts
into the fallopian/uterine tubes. The Mullerian ducts fuse at the
caudal end to form the uterus and top 1/3 of the vagina, remaining
unfused at the other ends to form the fallopian tubes which end
near the gonads/ovaries. Remnants also form the broad ligament,
which suspends the ovaries in the abdominal cavity
Slide 9
Overview: Female II X chromosomes only Stimulates Mullerian
duct growth Dax, Wnt4 Dax inhibits Sox9 (gonads), SRY expression in
XXY
Slide 10
Overview: Female 2 nd Sex Char. Ovarian estrogen Breast
development Genital development Increased body fat and
characteristic deposition Growth spurt: estrogen receptors in bone
Progesterone (after menarche) Breast development Ovarian/Adrenal
androgens Axillary and pubic hair GH (adenohypophysis) Increased
hip width
Slide 11
Kidney Development
Slide 12
Intermediate Mesoderm Becomes the suprarenal glands, gonads,
kidneys and associated tubes and vasculature
Slide 13
Timeline Day 18: intermediate mesoderm forms Day 24:nephrogenic
cord forms from intermediate mesoderm Day 26:urogenital ridge
(intermediate mesoderm) surrounds nephrogenic cords Day 28+
(pronephros) forms from cranial nephrogenic cords Day 28+ (wk4) to
Day 84 (week12)(meSonephros) forms from middle nephrogenic cords
Day 42- (wk6)meTanephros forms from caudal mesonephric ducts At
this time, sexual differentiation is also occuring Day 42 to 49
(wk6-7) cloaca(endoderm) separates to form rectum and bladder Day
112 (wk 16) metanephros has lobes and function as the collecting
ducts and ureter of the final kidney. The metanephric blastema
becomes the nephrons.
Slide 14
Timeline II-kidney Wk 40 Conception Pronephros, wk 4,
degenerates after a few days, useless Mesonephros (S for second) wk
4 to wk12, connects to blood vessels at wk 6-7 to function as
rudimentary kidney Metanephros (T for third), wk 6 onwards, buds
out from mesonephric duct, inducing the mesoderm around it
(metanephrogenic blastema) to become kidney renal tubules
(nephrons) while it becomes the ureter, renal pelvis, calyxes and
collecting duct system of the kidney.
Know the Nephros First, useless kidney, formed and
disintegrated at week 4 Part of mesonephros; the second, transitory
kidney (wk4) Joins with gonad medulla in males to become the male
reproductive tract (wk6). Third, final kidney, formed at week
6
Slide 17
The migrations of kidneys/gonads Kidneys go up/Gonads go down
Kidneys trade up for new arteries/Gonads take their arteries down
with them. Testes descend to the deep inguinal ring in week 12 At
month 7-9, testes continue to descend into the scrotum
Slide 18
Adrenal/Epinephrine glands Cortex forms from intermediate
mesoderm of the abdomen Medulla forms from migratory neural crest
sympathetic ganglia Chromaffin cells
Slide 19
Developmental Anomalies
Slide 20
Male Developmental Anomalies Hypospadius: urethra opens on the
underside/inferior side of the penis instead of through the center
of the glans. Can be panscrotal, penile or in the glans.
Epispadius: urethra opens on the superior side of the penis instead
of through the glans. Cryptoorchidism: Failure of the testes to
descend into the scrotum Associated with persistent Mullerian duct
syndrome Testicular hydrocele: fluid filled cysts in the scrotum
Indirect Inguinal Hernia MDs dont Lie (Indirect Inguinal hernias
happen to infants and are lateral to the inguinal ring)
(medial:direct)
Slide 21
Female Developmental Anomalies From not enough joining to too
much: Double uterus and vaginaDouble uterus Bicornate
uterusSeptated uterus NORMAL uterusCervical atresia Other:
unicornate uterus If only one Mullerian duct is presentNot enough
fusion of the Mullerian ducts Too much fusion of the Mullerian
ducts
Slide 22
External Genitalia
Slide 23
External Genitalia I Genital tubercle Male- glans penis and
corpus cavernosum Female- glans clitoris and clitoral crura and
shaft Urogenital Sinus Male , bulbourethral glands of Cowper,
prostate gland Female-, greater vestibular glands of Bartholin,
urethral and Skenes (paraurethral) glands Also forms the urethra,
bladder and allantois Urogenital Folds Male- ventral shaft of
penis, corpus spongiosum Female-labia minora, vesticular bulbs
Labioscrotal Folds Male-scrotum Female-labia majora
Slide 24
Urogenital Fold Genital Tubercle Labioscrotal swelling
Indifferent State (male=female) Primordial Phallus Anal Membrane
Urogenital membraneUrogenital Fold Labioscrotal swelling Cloacal
Membrane Becomes the ventral shaft of penis (corpus spongiosum) in
males Becomes the labia minora and vestibular bulbs in females
Becomes the glans penis and corpus cavernosum in males Becomes the
glans clitoris, crura and shaft of the clitoris in females Becomes
the scrotum in males Becomes the labia majora in females
Slide 25
Male Female Urogenital folds fuse to become the corpus
spongiosum of the penile shaft, the labioscrotal folds fuse to
become the scrotum. The genital tubercle sticks out at the end of
the penis as the glans penis. The rest of the genital tubercle
fuses with the urogenital folds to become the corpus
cavernosum.
Slide 26
External Genitalia II Male Induced by DHT Synthesis of DHT
requires 5-alpha reductase Female: lack of DHT
Slide 27
Summary: Wk 5: primordial germ cells (from yolk sac) migrate
into singular, undifferentiated gonad Wk 6: undifferentiated
genitalia in males, the medulla attaches to the mesonephric ducts
TESTES In females, the cortex attaches to the paramesonephric ducts
OVARY In both sexes, the cloaca septates into the bladder and
rectum The metanephros (future kidney) buds from the mesonephric
duct Wk 7: both Mullerian and Wolffian ducts are present Y (SRY)
chromosome induces testosterone stimulates testes formation (making
more testosterone/positive feedback) Stimulates Sertoli cells to
secrete Mullerian inhibiting factor Stimulates the growth of the
Wolffian ducts X chromosomes only Stimulates Mullerian duct growth
Wk 10: External Genitalia: DHT/5-aR for male differentiation
(female default)
Slide 28
Quiz Where do primordial germ cells come from? Yolk sac When do
they invade the undifferentiated gonad? Wk 5 What happens to the
undifferentiated gonad in males? Medulla joins with mesonephric
duct In females? Cortex joins with paramesonephric duct
Slide 29
Quiz II What forms from intermediate mesoderm? Gonads,
Wolffian/Mullerian ducts Upper 1/3 of vagina, uterus, fallopian
tubes, ovaries, broad ligament Testes, Seminal Vesicles,
Epidydimis, Ejaculatory Duct, Ductus Deferens, Gubernaculum
Basically everything except external genitalia Adrenal glands,
kidneys Associated vasculature
Slide 30
Quiz III What are the undifferentiated precursors of external
genitalia? (and the prostate which is internal) Genital tubercle-
glans penis/clitoris, crura and shaft of the clitoris, corpus
cavernosum of the penis Urogenital Sinus- bulbourethral glands of
Cowper, prostate gland in the male, greater vestibular glands of
Bartholin, urethral and Skenes (paraurethral) glands in the female.
Also develops into the bladder, urethra and allantois. Urogenital
Folds- ventral shaft of penis, corpus spongiosum,labia minora,
vesticular bulbs Labioscrotal folds- labia majora, scrotum What do
they become?
Slide 31
Quiz III What genes cause male gonadal differentiation? SRY,
Sox9 What allow Wolffian duct proliferation? Testosterone, MIF/AMH
What causes male external genitalia differentiation? DHT, requiring
5-alpha reductase What genes cause female gonadal differentiation?
Dax inhibits Sox9, absence of SRY What causes female external
genitalia differentiation? Lack of DHT
Slide 32
Bibliography Class Notes Podcast First Aid Wikipedia
