Sexual Differentiation - Anatomy & Physiology

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Genetic Sex

  • Established at the time of fertilisation.
  • The foetus receives its genetic endowment in two equal portions from the male gamete (Spermatozoon) and female gamete (Oocyte).
  • The X sex chromosome is larger than the Y sex chromosome.
  • Females have XX chromosomes. All oocytes contain one X chromosome, they are the homogametic sex.
  • Males have XY chromosomes. Spermatozoa form two distinct populations, one containing X chromosomes and one containing Y chromosomes. They are the heterogametic sex.


  • The Y chromosome is required to initiate male development.
  • In absence of the Y chromosome, female gonads (Ovaries) will develop.
  • The prime male determining gene is SRY (sex determining region of the Y chromosome.
  • SRY is a very small piece of DNA that acts as a molecular switch to regulate structural genes and autosomal chromosomes, determining if and when they are to be activated.
  • The presence of SRY alone is sufficient to ensure development of male gonads (Testes).
  • Female is the default sex, in absence of SRY female gonads (Ovaries) will develop.


  • Subsequent gonadal development is dependent on a normal population of germ cells.
  • Normal Oocyte growth requires the activity of both X chromosomes.
  • Normal Spermatogenesis requires the activity of no more than one X chromosome.


  • Early development of gonads proceeds similarly in both sexes. The gonads are derived from two distinct tissues:
    • Somatic mesenchymal tissue forms the matrix of the gonad
    • Primordial germ cells form the gametes


  • Genital ridge forms from somatic mesenchyme.
  • Primordial germ cells migrate to the genital ridge.
  • At this stage it is not possible to discriminate between male and female gonads.
  • Y chromosomal determination of gonadal sex is only visible when primordial germ cell colonisation is complete.


MALE

  • Sex cord cells proliferate to form the testes cord. During this period SRY is expressed for the first time within Sertoli cells (SRY is NOT expressed in primordial germ cells).
  • Sex cords with a basement membrane become Semniferous Cords which give rise to Semniferous Tubules.
  • Within the semniferous cords are two cell populations:
    • Primordial germ cells - Prospermatogonia which give rise to Spermatozoa
    • Mesodermal cord cells which give rise to Sertoli cells
  • Between cords, the loose mesenchyme undergoes vascularisation and develops as stromal tissue.
  • Within the stromal tissue, cells condense into clusters to form specialized endocrine units - the interstitial Leydig Cells


FEMALE

  • At the time the male gonad is undergoing marked changes under the direction of SRY, the female gonad continues to appear indifferent and does not express SRY.
  • Small clusters of mesenchyme surround the germ cells to initiate formation of Primary Follicles, characteristic of the Ovary.
  • In follicles:
    • Mesenchymal cells give rise to Granulosa cells
    • Germ cells give rise to Oocytes


Foetal sex differentiation

  • Endocrine activity of the Ovaries is NOT essential for sex differentiation during foetal life, abnormal ovarian development will have no effect until puberty.
  • Testes secrete two essential hormones:
    • Steroidal hormones (mainly C19 androgens) from Leydig cells
    • Mullarian Inhibiting Hormone (MIH) also known as Anti-Mullarian Hormone (AMH) from Sertoli Cells
  • In absence of these testicular hormones, female differentiation occurs.
  • Thus, sexual differentiation must be actively diverted down the male route, the female route requires no active intervention.

Internal Genetalia

  • Male: Wolffian Duct developes from the Mesonephric Duct
  • Female: Mullarian Ducts develop from the Paramesonephric Duct
  • This is dependent on appropriate hormonal influence.


MALE

  • MIH from Sertoli cells and Androgens from Leydig cells prevent spontaneous development of female internal genetalia.
  • Androgens actively maintain Wolffian Ducts, which give rise to male internal genetalia:
    • Epididymis
    • Vas Deferens
    • Vesicular Glands/ Seminal Vesicles
  • MIH causes Mullarian Ducts to regress


FEMALE

  • Wolffian Ducts spontaneously regress in absence of Androgens.
  • Mullarian Ducts persist to give rise to female internal genetalia:
    • Oviducts
    • Uterus
    • Cervix
    • Cranial Vagina
  • Normal Ovarian activity is NOT essential for the development of normal female internal genetalia.

External Genetalia

Turner's Syndrome
Kleinfelter's Syndrome
Testicular Feminisation
Adrenogenital Syndrome
Hermaphroditism
Bovine Freemartinism