Animal Science 434 Reproductive Physiology

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Animal Science 434Reproductive Physiology

• Lec 5 Embryogenesis of the Pituitary and Sexual
  Development

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Development of the Pituitary Gland
Infundibulum
Brain
Rathkes Pouch
Stomodeum
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Germ Cell Migration
Migration begins by the 4 week of gestation in
cow and human.
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Migration from endoderm through mesoderm.
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In birds the migration is via the blood stream.
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Fetal Kidneys

• Pronephros
• regresses
• Mesonephros
• portions of reproductive tract
• Metenephros
• Adult kindney and urinary ducts

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Development of Mesenephros and Metenephros
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Jost Experiments
Mesonephric Ducts (Wolffian Ducts)
Paramesonephric Ducts (Mullerian Ducts)
Testis
Ovary
Epididymis
Epididymis
Oviduct
Vas Deferens
Seminal Vesicles
Uterus
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Sex Determination The Jost Paradigm
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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

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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.

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Human X and Y Chromosomes
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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

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The Y Chromosome Cont.

• B. Other genes on the Y chromosome
• Spermatogenesis
• androgen production
• long bone growth

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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

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Gonadal Sex
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Testis Determining Factor (SRY gene product)
XY Male
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Testicular Development
Mesonephric Tubules
Mesonephric Duct (Wolffian Duct)
Rete Tubules
Mullerian Duct
Tunica Albuginea
Undifferentiated Sex Chords
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Mesonephric Tubules
Rete Tubules
Wolffian Duct

• Primary, Epithelial or
• Medullary Sex Chords
• Primordial germ cells (gonocytes)
• Pre-Sertoli Cells

Mullerian Duct
Tunica Albuginea
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Primary Sex Chords in Fetal Testis
Pre-Sertoli
Gonocyte
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Hormonal Sex
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Testis Determining Factor (SRY gene product)
XY Male
Testes develop
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Wolffian Duct Cells
Nucleus
T
Testis
T
TR
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Rete Tubules
Efferent Ducts (Vas Efferentia)
Epididymis
Seminiferous Tubules
Vas Deferens
Tunica Albuginea
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Testis Determining Factor (SRY gene product)
XY Male
Testes develop
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Vas efferentia
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Female Development
No TDF
Testes Determining Factor
XX Female
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Ovarian Development
Regressing Tubules
Mullerian Duct
Primary or Epithelial Sex Chords
Future Ovarian Cortex
Wolffian Duct
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Regressing Tubules
Mullerian Duct
Regressing Epithelial Sex Chords
Future Ovarian Cortex
Regressing Wolffian Duct
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Regressing Tubules
Primordial Follicles
Mullerian Duct
Regressing Epithelial Sex Chords
Future Ovarian Cortex
Regressing Wolffian Duct
Secondary or Cortical Sex Chords (egg nests)
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Primordial Follicles
Mullerian Duct
Ovarian Medulla
Ovarian Cortex
Regressing Wolffian Duct
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2nd Sex Chords in Fetal Ovary
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Development of the Uterus, Cervix and Vagina
Mullerian Duct
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Fused Mullerian Duct
Hymen
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Reproductive tract develops outside
the peritoneum!
Broad Ligament Development (transverse anterior
section)
Ovary
Regressing Wolffian Duct
Mullerian Duct
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Ovary
Regressing Wolffian Duct
Mullerian Duct
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(Posterior Transverse Section)
Genital Fold (Future Broad Ligament)
Regressing Wolffian Duct
Mullerian Duct
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Testis Determining Factor (SRY gene product)
No TDF
XX Female
XY Male
Testes develop
Ovaries Develop
No AMH
No Testosterone
Sertoli cells secrete anti-mullerian hormone (AMH)
AMH causes leydig cells to differentiate
Degeneration of Mullerian duct
Mullerian ducts become the oviducts, uterus,
cervix and part of the vagina
Degeneration of Wolffian duct
Testosterone
Development of male duct system
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Phenotypic Sex
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Testis Determining Factor (SRY gene product)
XY Male
Testes develop
Sertoli cells secrete anti-mullerian hormone (AMH)
AMH causes leydig cells to differentiate
Degeneration of Mullerian Duct
Testosterone
Development of male duct system
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Wolffian Duct Cells
Nucleus
T
Testis
T
TR
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Accessory Sex Glands and External Genitalia Cells
Nucleus
T
Testis
D
T
DR
5??- Reductase
Prostate, Cowpers Gland
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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 5a-reductase

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External Genitalia Differentiation
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Testis Determining Factor (SRY gene product)
No TDF
XX Female
XY Male
Testes develop
Ovaries Develop
No AMH
No Testosterone
Sertoli cells secrete anti-mullerian hormone (AMH)
AMH causes leydig cells to differentiate
Degeneration of Mullerian duct
Mullerian ducts become the oviducts, uterus,
cervix and part of the vagina
Degeneration of Wolffian duct
Testosterone
Development of male duct system
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Brain or Behavioral Sex
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Brain and Behavioral Sex Differentiation
Genetics
Gonadal Steroid Hormones
Sexual Behavior
Brain Structure
Experience
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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

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Descent of the Testis into the Scrotum
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Testicular Descent
Fusion of the tunica albuginea and peritoneum to
form the visceral tunica vaginalis
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Spermatic Artery
Front View
Fusion of Peritoneum and Gubernaculum
Testis
Gubernaculum
Peritoneum
Inguinal Ring
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Rapid growth of gubernaculum
Spermatic Artery
Peritoneum
Visceral Growth
Visceral Growth
Inguinal Ring
Testis
Peritoneum
Gubernaculum (rapid growth)
Parietal Tunica Vaginalis
Testis is pulled down to the inguinal ring.
Visceral Tunica Vaginalis
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Gubernaculum regresses
Testis pulled into scrotum
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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
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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

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Normal Dog Seminiferous Tubule
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Cryptorchid Dog Seminiferous Tubule
SertoliCells
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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

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Inguinal Hernia
Loop of Intestine
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Abnormalities in Development
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The Freemartin in Cattle

• Female born twin to a bull
• Placenta membranes of the 2 fetuses fuse
• Common blood supply
• At time of testis formation
• Before ovarian formation
• Both fetuses share a common hormone milieu
• testosterone
• anti-mullerian hormone
• Animals are chimeric (WBC from other twin)
• TDF (SRY) expressed in both individuals

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Normal
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Freemartin
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Normal Vs. Freemartin
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Freemartin

• AMH from bull - blocks Mullerian ducts
• Posterior vagina, no anterior vagina
• Testosterone from bull
• clitoral enlargment
• Brain changes like that of male
• Ovaries do not grow but are chimeric
• Ovotestis
• SRY and therefore AMH and Testosterone
• Further changes and adult male behavior
• Use as estrus detector
• Abnormalities exist as a continuum

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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

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Testicular Feminization
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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

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Guevedoces Development
Normal tissue dependent upon testosterone is
shown in black.