Sex differentiation

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Normal development

  • Early development of the gonad proceeds identically in both sexes
  • Two distinct tissues will give rise to the gonads:
    1. Somatic mesenchymal tissues
      • form the matrix of the gonad
      • Gives rise to the primitive gonadal ridge
      • Columns of cells derived from a superficial epithelium overlying the primitive gonadal ridge penetrate the tissue to form primitive sex cords
    2. primordial germ cells
      • migrate from outside the embryo and then colonize this matrix to form the gametes
      • arise outside the genital ridge region
      • multiply by mitosis and then migrate by an amoeboid action from the yolk sac through the hind gut and come to lie within and between the developing sex cords in the primitive gonadal ridge
  • The morphologic differentiation of the ovary and testis is dependent upon whether or not the Y-chromosome is expressed.

Abnormal development

  • Turner's syndrome provides insight into early development:
    1. Women with Turner's syndrome develop an ovary in spite of being germ cell deficient
    2. Subsequently, the germ cells die and abnormal ovarian development occurs
    3. a highly regressed ovary is present in such women
    4. This shows that it is not necessary to have 2 X-chromosomes to initiate ovary formation (simply the lack of a Y-chromosome will suffice)
    5. Also, it is necessary to have 2 X-chromosomes to complete ovarian development.

Differentiation of the internal genitalia

  • The main role of the Y-chromosome in sex determination is complete with the establishment of the gonad in the fetus
  • From this point onward the gonads will assume a pivotal position in the rest of sexual differentiation both pre- and postnatally
  • In utero, the testis becomes the critical organ in this development
  • The testes actively secrete two essential hormones:
    1. The Leydig cells secrete androgens
    2. The Sertoli cells in the seminiferous tubules secrete a glycoprotein hormone called the Mullerian inhibiting hormone or the Mullerian regression hormone (MIH, MRH)
  • The internal genitalia do not develop from one indifferent primordium but instead from two separate sets of primitive ducts (Wolffian and Mullerian ducts)
  • In the female:
    • the Wolffian duct naturally regresses
    • the Mullerian duct persists and develops to give rise to the oviducts, uterus, cervix and the upper portion of the vagina
  • In the male:
    • the two testicular hormones prevent this inherent trend towards the development of female duct systems
    • The androgens induce the Wolffian ducts to develop and give rise to the epididymis, vas deferens and seminal vesicles
    • The testicular androgens have no influence on the Mullerian duct system, but normal regression of this duct in males is caused by the second testicular hormone MIH or MRH

Differentiation of the external genitalia

  • As with the internal genitalia, the equipment that forms the external genitalia is bipotential, and can form either male or female tools.

Abnormalities

Testicular feminization

  • A situation in which the individual lacks biologically effective receptors for androgens, and so are genotypically male, but phenotypically female

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