Transcript Embryogenesis of the pituitary gland, sexual differentiation of the

Animal Science 434
Reproductive Physiology
Lec 5: Embryogenesis of the Pituitary and
Sexual Development
Development of the Pituitary Gland
Infundibulum
Brain
Stomodeum
Rathke’s Pouch
Germ Cell Migration
Migration begins by the 4 week of gestation in cow and human.
Migration from endoderm
through mesoderm.
In birds the migration is via the blood stream.
Fetal Kidneys
•
Pronephros
•
Mesonephros
•
» regresses
» portions
of reproductive tract
Metenephros
» Adult
kindney and urinary ducts
Development of Mesenephros and Metenephros
Jost Experiments
Mesonephric Ducts
Paramesonephric Ducts
(Wolffian Ducts)
(Mullerian Ducts)
Ovary
Testis
Epididymis
Oviduct
Uterus
Epidi
Vas
Deferens
dymi
Seminal
s
Vesicles
Sex Determination: The Jost Paradigm
Chromosomal Sex
Chromosomal Sex
Gonadal Sex
Gonadal Sex
Hormonal Sex
Phenotypic Sex
Phenotypic Sex
Brain and/or Behavioral Sex
Chromosomal Sex
• Single Pair of sex chromosomes
•
•
•
» mammals, some but not all vertebrates
Sex is environmentally determined
» sea worms, fish, reptiles
Multiple sex chromosomes
» invertebrates, insects, reptiles
Haplodiploidy
» bees, spiders
Chromosomal Sex
A. Drosophila
• Sex depends on the number of X chromosomes
– X or XY or XO = Male
– XX or XXX or XXY = Female
B. Human (mammals)
• XY or XXY or XXYY or XXXY = Male (testis)
• XX or XXX = Female (ovary)
• XO = Female with incomplete ovarian development
• XXY or XXYY or XXXY or XXXXY = testis but
impaired sperm production
C. Conclusion
• The gene that controls testicular differentiation is
on the Y chromosome in mammals.
Human X and Y Chromosomes
The Y Chromosome
A. Region coding for testicular development
• Short arm of Y chromosome
–H-Y Antigen
« no longer believed to be involved
–SRY
« Codes for a DNA binding protein
« acts as a transcription factor
« Causes
•primary sex chord (seminiferous tubule)
development
•Anti-Mullerian Hormone production
•Testosterone production
« absence of SRY
•2nd sex chords (egg nests) develop
The Y Chromosome Cont.
B. Other genes on the Y chromosome
» Spermatogenesis
» androgen production
» long bone growth
SRY and Birds
•
•
Birds
» females ZW, males ZZ
» W chromosome determines sex
» SRY is found on the Z chromosome
!
SRY is not the only sex determining gene in
animals
Gonadal Sex
XY Male
Testis Determining Factor
(SRY gene product)
Testes develop
Testicular Development
Mesonephric Duct
(Wolffian Duct)
Mesonephric Tubules
Rete Tubules
Mullerian Duct
Tunica
Albuginea
Undifferentiated
Sex Chords
Mesonephric
Tubules
Rete Tubules
Wolffian
Duct
Mullerian Duct
Primary, Epithelial or
Medullary Sex Chords
Tunica
• Primordial germ cells
Albuginea (gonocytes)
• Pre-Sertoli Cells
Primary Sex Chords in Fetal Testis
Pre-Sertoli
Gonocyte
Hormonal Sex
XY Male
Testis Determining Factor
(SRY gene product)
Testes develop
Sertoli cells secrete
anti-mullerian hormone (AMH)
AMH causes leydig
cells to differentiate
Testosterone
Development of male
duct system
Wolffian Duct Cells
Nucleus
Testis
T
T
TR
Efferent Ducts
Rete Tubules
(Vas Efferentia)
Epididymis
Vas
Deferens
Seminiferous
Tubules
Tunica
Albuginea
XY Male
Testis Determining Factor
(SRY gene product)
Testes develop
Sertoli cells secrete
anti-mullerian hormone (AMH)
AMH causes leydig
cells to differentiate
Testosterone
Development of male
duct system
Degeneration of
Mullerian duct
Vas efferentia
Female Development
XX Female
No TDF
Testes Determining Factor
Ovaries Develop
No
Testosterone
Wolffian Ducts
Regress
No AMH
Mullerian ducts become
the oviducts, uterus, cervix
and part of the vagina
Ovarian
Development
Regressing
Tubules
Mullerian
Duct
Primary or
Epithelial
Sex Chords
Future Ovarian
Cortex
Wolffian
Duct
Regressing
Tubules
Mullerian
Duct
Regressing
Epithelial
Sex Chords
Future Ovarian
Cortex
Regressing
Wolffian
Duct
Regressing
Tubules
Primordial
Follicles
Mullerian
Duct
Regressing
Epithelial
Sex Chords
Future Ovarian
Cortex
Regressing
Wolffian
Duct
Secondary or
Cortical Sex
Chords
(egg nests)
Primordial
Follicles
Mullerian
Duct
Ovarian
Medulla
Regressing
Wolffian
Duct
Ovarian
Cortex
2nd Sex Chords in Fetal Ovary
Development
of the Uterus, Cervix
and Vagina
Mullerian Duct
Fused Mullerian
Duct
Hymen
Reproductive tract develops outside the
peritoneum!
Broad Ligament Development
(transverse anterior section)
Ovary
Regressing
Wolffian Duct
Mullerian
Duct
Ovary
Regressing
Wolffian
Duct
Mullerian
Duct
(Posterior Transverse Section)
Genital Fold
(Future Broad Ligament)
Regressing
Wolffian
Duct
Mullerian
Duct
Testis Determining Factor
(SRY gene product)
XX Female
XY Male
Testes develop
Sertoli cells secrete
anti-mullerian hormone (AMH)
AMH causes leydig
cells to differentiate
Testosterone
Development of male
duct system
No TDF
Degeneration of
Mullerian duct
Ovaries Develop
No
Testosterone
Degeneration of
Wolffian duct
No AMH
Mullerian ducts
become
the oviducts,
uterus, cervix
and part of the
vagina
Phenotypic Sex
XY Male
Testis Determining Factor
(SRY gene product)
Testes develop
Sertoli cells secrete
anti-mullerian hormone (AMH)
AMH causes leydig
cells to differentiate
Degeneration of
Mullerian Duct
Testosterone
Dihydrotestosterone
Development of male
duct system
Development of penis
scrotum and accessory
sex glands
Wolffian Duct Cells
Nucleus
Testis
T
T
TR
Accessory Sex Glands* and External
Genitalia Cells
Nucleus
Testis
T
T
D
5Reductase
DR
*Prostate, Cowper’s Gland
Significance of DHT
•
Androgen receptor has a higher affinity
for DHT
•
Can get effects with low levels of
circulating testosterone
•
Secondary sex characteristic tissue in
the male expresses 5-reductase
External Genitalia Differentiation
Testis Determining Factor
(SRY gene product)
No TDF
XX Female
XY Male
Testes develop
Ovaries Develop
No
Testosterone
Sertoli cells secrete
anti-mullerian hormone (AMH)
AMH causes leydig
cells to differentiate
Degeneration of
Mullerian duct
Degeneration of
Wolffian duct
Testosterone
Dihydrotestosterone
Development of male
duct system
Development of penis
scrotum and accessory
sex glands
No AMH
Mullerian ducts
become
the oviducts,
uterus, cervix
and part of the
vagina
Brain or Behavioral Sex
Brain and Behavioral Sex Differentiation
Genetics
Gonadal
Steroid
Hormones
Brain
Structure
Experience
Sexual
Behavior
Brain Sexual Differentiation
•
•
•
Rat female
» Give testosterone shortly after birth
–
fail to copulate or cycle like female as adult
Sexually dimorphic nucleus
Human male and female differences in behaviors
» aggression
» childhood play
» 3D visual rotation
Descent of the Testis
into the Scrotum
Testicular Descent
Fusion of the tunica
albuginea and
peritoneum
to form the visceral
tunica vaginalis
Front View
Fusion of
Peritoneum
and
Gubernaculum
Spermatic Artery
Testis
Gubernaculum
Peritoneum
Inguinal Ring
Rapid growth
of
gubernaculum
Spermatic Artery
Peritoneum
Visceral Growth
Testis
Gubernaculum
(rapid growth)
Testis is
pulled down
to the inguinal
ring.
Visceral Growth
Inguinal Ring
Peritoneum
Parietal Tunica
Vaginalis
Visceral Tunica
Vaginalis
Gubernaculum
regresses
Testis pulled into
scrotum
Continued regression of
Gubernaculum
Testis pulled deeper
into Scrotum
Vaginal Process
attaches to Scrotum
Space between
Visceral and Parietal T.V.
is continuous with
Peritoneum
Failure or Problems With
Testicular Descent
•
Cryptorchid - highly heritable
» Unilateral or bilateral
– Germ cells fail to multiply and then die, sertoli
cells only in seminferous tubules
» High percentage develop testicular cancer
» Surgical correction possible but does not
reduce cancer risk
Normal Dog Seminiferous Tubule
Cryptorchid Dog Seminiferous Tubule
Sertoli
Cells
Failure or Problems With
Testicular Descent
•Cryptorchid - highly heritable
–Unilateral or bilateral
•Germ cells fail to multiply and then die,
sertoli cells only in seminferous tubules
–High percentage develop testicular
cancer
–Surgical correction possible but does not
reduce cancer risk
• Inguinal Hernia
Inguinal Hernia
Loop of
Intestine
Abnormalities in Development
The Freemartin in Cattle
•
•
•
Female born twin to a bull
Placenta membranes of the 2 fetuses fuse
Common blood supply
•
Both fetuses share a common hormone milieu
•
» At time of testis formation
» Before ovarian formation
» testosterone
» anti-mullerian
hormone
Animals are chimeric (WBC from other twin)
» TDF
(SRY) expressed in both individuals
Normal
Freemartin
Normal Vs. Freemartin
Freemartin
•
AMH from bull - blocks Mullerian ducts
•
Testosterone from bull
» Posterior
vagina, no anterior vagina
» clitoral enlargment
» Brain changes like that
of male
•
Ovaries do not grow but are chimeric
•
•
Use as estrus detector
Abnormalities exist as a continuum
» Ovotestis
– SRY and therefore AMH and Testosterone
– Further changes and adult male behavior
Testicular Feminization in an XY Individual
•
•
•
•
•
No androgen receptor
Testis
No testosterone response so no Wolffian duct
development
AMH present so mullerian ducts regress
External genitalia is female due to lack of
androgen
Testicular
Feminization
5 Reductase Deficiency in an XY Individual
•
•
•
•
•
•
Guevedoces (penis at 12)
testis
AMH present so Mullerian ducts regress
Wolffian ducts
psuedovagina and female external
genitalia
at puberty may differentiate into more
of a phenotypic male
Guevedoces Development
Normal tissue dependent upon testosterone is
shown in black.