Sexual Differentiation - Anatomy & Physiology

Overview of Sexual Differentiation,Copyright RVC 2008

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.
• SRY encodes the protein Testes Determining Factor (TDF)
• 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's 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's 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.