Embryogenesis of the Pituitary Gland, Sexual Differentiation of the Male and Female

Reading

• Chapter 4
• Handout 3
• Any additional lecture diagrams not in text

Development of the Pituitary Gland

• Anterior Pituitary
  • develops from Rathke's pouch which is an outgrowth of the embryonic mouth
• Posterior Pituitary
  • the base of the embryonic brain called the infundibulum grows down to meet the developing Rathke's pouch
• Sella Turcica
  • a depression in the sphenoid bone which surround the anterior and posterior pituitary

Germ Cell Migration

• They originate from ectodermal cells of the inner cell mass of the embryo.
• They are first identifiable in the endoderm of the yolk sac placenta.
• Migration occurs around the fourth week of gestation in cow and human, with movement of the germ cells to the genital ridge by passing through the mesoderm. In birds, migration of germ cells occurs through the blood stream.

Fetal Kidneys

• Pronephros
• Mesonephros
• Metenephros

Sexually Indifferent Stage

• mesonephric kidney - gonad
• mesonephic duct - Wolffian duct in male
• pramesonephric duct - Mullerian duct in female

The Jost Paradigm

• chromosomal sex, gonadal sex, phenotypic sex
• chromosomal sex, gonadal sex, hormonal sex, phenotypic sex, brain and/or behavioral sex

Chromosomal Sex

• environmentally determined
• single pair of sex chromosomes
• multiple sex chromosomes
• haplodiploidy

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 or XXXXY = 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 primary gene that controls testicular differentiation is on the Y chromosome in mammals.

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 or assists other transcription factors
  • the gene products which are transcribed regulate primary sex chord differentiation (formation of seminiferous tubules), androgen production and Antimullerian hormone (AMH)
  • in the absence of the SRY protein, primary sex chord regress and secondary sex chords (egg nests) develop

B. Other genes on the Y chromosome

• many genes are found on the Y chromosome with some involved in spermatogenesis, androgen production and long bone growth

Problems With SRY as the Male Determining Gene

• Transgenic mice studies find that expression of SRY leads to formation of testis and an apparently normal male reproductive tract but there is no spermatogenesis
• In birds, sex is determined by the presence of the W chromosome in females (females ZW, males ZZ) but SRY is found on the Z chromosome

Gonadal and Hormonal Sex

A. Differentiation of the Testis and Male Tract

• Testis formation is under control of SRY
• As germ cell migration is occurring, SRY expression causes the mesoderm of the genital ridge to differentiate into Sertoli cells. In addition primary, epithelial or medullary sex chords form, Sertoli cells move into these sex chords along with the undifferentiated germ cells, and the seminiferous tubules are formed. The germ cells then divide mitotically but do not begin meiosis until puberty.
• Sertoli cells secret Antimullerian Hormone (AMH) which causes
  • differentiation of Leydig cells
    • secretion of testosterone
      • acts by binding to testosterone receptor in nucleus of target cells and triggers developmental changes
      • differentiation of the Wolffian duct cells to become vas efferentia, epididymis, vas defferens and seminal vesicles
  • causes Mullerian ducts to regress

B. Differentiation of the Ovary and Female Tract

• In absence of SRY, medullary sex chords regress and cortical or secondary sex chords form. The mesoderm develops into granulosa cells and these along with germ cells migrate into the sex chords to form the egg nests. The germ cells initially divide mitotically but very soon enter meiosis. Meiosis however is not completed and the oocytes arrest further development until after puberty when an LH rise triggers ovulation.
• Since mesoderm cells develop into the granulosa cells, sertoli cells are not formed and AMH is not produced
  • Mullerian ducts develop
    • forms oviduct, uterine horns, uterine body, cervix and anterior vagina
    • outgrowth of urogenital sinus meets Mullerian duct to form the posterior vagina
      • hymen is present at junction of anterior and posterior vagina
• Lack of testosterone production leads to regression of Wolffian ducts

C. Gonad and reproductive tracts develop outside of peritoneum.

Phenotypic Sex

• Differentiation of the Accessory Glands in male
  • Requires conversion of testosterone to dihydrotestosterone in target cells
• Differentiation External Genitalia
  • Male - Penis, scrotum
    • requires conversion of testosterone to dihydrotestosterone in target cells
  • Female - Clitoris, labia
    • lack of testosterone leads to female pattern of development

Descent of the Testis

• During initial development pushes into peritoneal cavity
  • fusion of tunica albuginea and visceral tunica vaginalis
• Gubernaculum grows down through inguinal ring
  • expands scrotum
  • pulls testis down into scrotum
• Regression of gubernaculum
  • testis is pulled deeper into scrotum
  • vaginal process attaches to scrotum
  • space between visceral and parietal tunica vaginalis is continuous with peritoneum
• Problems
  • cryptorchid, unilateral or bilateral
  • inguinal hernia

Brain or Behavioral Sex

• exposure of the brain to sex steroids during fetal development sets the pattern for responses as an adult to external stimuli and hormonal production

Abnormalities in Development

A. 5a-Reductase Deficiency in an XY Individual

• lack 5a-Reductase and so can not make testosterone into dihydrotestosterone
• testis, AMH, some Wolffian ducts
• psuedovagina, female external genitalia
• at puberty may differentiate into phenotypic male

B. Testicular Feminization in an XY Individual

• no androgen receptor
• testis is present along with AMH
• no Wolffian or Mullerian duct development
• external genitalia is female

C. Freemartin in Cattle

• female born twin to a bull
• placenta fuses so that twins share a common blood supply and hormone milieu
  • testosterone
  • AMH
• animals are chimeric
  • both express testis determining factor

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