Gonadal embryology

Gonadal Genesis

See: Mal-descent of the testis

Overview

• Three structures comprise the gonad:
  • Primordial Germ Cells - Migrate to Gonadal Ridge from Yolk Sac
  • Genital Ridge (Mesenchyme of mesonephros)
  • Coelomic Epithelium
• Steps overview
  • 4 weeks - formation of genital ridge
  • 6 weeks - migration of primordial germ cells
  • 7 weeks - Differentiation into testes of ovaries (SRY gene)
  • 8-10 weeks - Gonadal development
  • 10-12 weeks - Maturation

Weeks 4-6

• Initial Development and Formation of Genital Ridges
  • Genital Ridge Formation
    • Around week 4, the genital ridges (future gonads) begin to form along the mesonephros in the intermediate mesoderm.
      • These undifferentiated ridges will later give rise to either testes or ovaries.
  • Primordial Germ Cells Migration
    • Primordial germ cells (PGCs), which are precursors to gametes, migrate from the yolk sac to the genital ridges by week 6, settling in the developing gonads.

Week 7

• Differentiation into Testes or Ovaries
  • Genetic Determination
    • The genetic sex (XX for female, XY for male) begins to influence the differentiation pathway.
  • SRY Gene Activation (if XY)
    • In the presence of the SRY (Sex-determining Region Y) gene, the undifferentiated gonads start developing into testes.
    • Sertoli cells begin to form and produce Anti-Müllerian Hormone (AMH), which suppresses the development of female reproductive structures.
  • Absence of SRY (if XX)
    • In the absence of the SRY gene, the gonads develop into ovaries.
    • There is no AMH production, allowing the Müllerian ducts to persist, which will form female reproductive structures (fallopian tubes, uterus, upper vagina).

Weeks 8-10

• Testis Development (if XY):
  • Sertoli cells further differentiate, organizing around the germ cells to form testis cords, which will later develop into seminiferous tubules.
  • Leydig cells appear and start producing testosterone, promoting the development of male external genitalia and the Wolffian duct system (epididymis, vas deferens, and seminal vesicles).
• Ovary Development (if XX):
  • The absence of AMH allows the Müllerian ducts to continue developing.
  • Oogonia (female germ cells) start proliferating and differentiate into primary oocytes within developing ovarian follicles.

Weeks 10-12

• Further Maturation
  • Male Gonads (Testes)
    • By week 10, testosterone production helps masculinize external genitalia, while AMH ensures regression of the Müllerian ducts.
  • Female Gonads (Ovaries)
    • By week 12, oogonia cease proliferation and enter meiosis, halting at the primary oocyte stage, which will remain dormant until puberty.

Supporting structures

Mesonephric duct (Wolffian duct)

• Derivates of Mesonephric Duct
  • Canal of Epididymis
  • Vas Deferens
  • Ejaculatory Duct
• The mesonephric ducts develop alongside the mesonephros (an early kidney structure)
• In males, the mesonephric ducts are preserved and differentiate into reproductive structures under the influence of testosterone produced by Leydig cells and Anti-Müllerian Hormone (AMH) produced by Sertoli cells.

Paramesonephric duct (Müllerian duct)

• Forms
  • Fallopian Tubes: The upper portions of the ducts form the fallopian tubes.
  • Uterus: The middle portions of the ducts fuse at the midline to form the uterus.
  • Cervix and Upper Vagina: The lower portions of the fused ducts become the cervix and the upper part of the vagina.
• In men
  • Appendix Testis

Mesonephric Tubules

• Derivates of remaining Mesonephric Tubules
  • Vasa Efferentia of Testis
  • Paradidymis

Mesorchium

• Double peritoneal fold suspending the testis
• Upper fold transmits spermatic vessels
• Lower fold: Gubernaculum
  • Gubernaculum
    • Condensation of Mesodermal cells connecting lower pole of Testis to region of anterior abdo wall that layer forms the Scrotum
    • Abnormal insertion of the Gubernaculum
      • Leads to ectopic testis (cf undescended testis or cryptorchidism

Processus Vaginalis

• Sac of peritoneum that protrudes down the inguinal canal anterosuperior to the Gubernaculum

Gonadal Descent

Phase 1: Transabdominal Descent (Weeks 8-15)

• Descent Toward the Inguinal Region
  • Week 8 - testes are in the upper abdomen near the kidney.
  • Weeks 10 and 15 - begin descending toward the inguinal region
    • Pulled down by the shortening of the gubernaculum and influenced by anti-Müllerian hormone (AMH) from Sertoli cells
      • Gubernaculum – a condensation of mesodermal cells connecting the lower pole of the Testis to the region of the anterior abdominal wall that later forms the Scrotum
      • Traverses the site of the future Inguinal Canal
• Peritoneum and Processus Vaginalis
  • The peritoneum forms a pouch, the processus vaginalis, which follows the gubernaculum into the inguinal canal. This will eventually become part of the covering around the testes in the scrotum.

Phase 2: Inguinoscrotal Descent (Weeks 25-35)

• Descent through the Inguinal Canal:
  • Week 25 - testes start their journey through the inguinal canal.
    • This phase is androgen-dependent, relying on testosterone production from Leydig cells.
• Final Descent into the Scrotum:
  • Weeks 33-35 - the testes have usually descended fully into the scrotum.
    • The processus vaginalis typically closes, leaving a small serous pouch (the tunica vaginalis) around each testis in the scrotum.
      • 50-75% of infants have complete closure at birth
      • Most of the remaining will close over the next 12 months
      • Failure of obliteration of processus vaginalis leads to
        • Hydrocele, Hernia, Encysted hydrocele of the cord
      • Right testis descends later than left
        • ↑ Incidence of abnormalities on R side
        • ↑ Incidence of hernias in premature babies
      • Normal post-partum intra-abdominal pressures make it more difficult for the processus to close spontaneously