Development of the reproductive system (Differentiation of the sexual organs)

Summary

The development of the reproductive system begins with the formation of undifferentiated gonads and the paired mesonephric and paramesonephric ducts. Further differentiation of the gonads is dependent on the presence or absence of the SRY gene on the Y chromosome, which stimulates differentiation of the testes in males. Testosterone (produced by Leydig cells) drives the differentiation of the mesonephric ducts into male internal sex organs and dihydrotestosterone drives the differentiation of male external genitalia. Mullerian inhibitory factor (MIF, produced by Sertoli cells) suppresses the differentiation of the paramesonephric ducts. In females, the absence of MIF allows differentiation of the paramesonephric ducts into the female internal organs, and estrogen drives the differentiation of female external genitalia. The absence of testosterone prevents the differentiation of the mesonephric ducts in females. The descent of the gonads, which is much more prominent in males, is facilitated by the gubernaculum, which promotes the descent of the testes from their initial retroperitoneal location into the scrotum.

Overview of sexual differentiation

Timeline [1]

Components [2][3]

Gonadal sex differentiation

References: [3]

Ductal sex differentiation

Embryonic structure General description [2][4][3]

Males (starting the 7th week)

Females (starting the 8th week)

Paramesonephric ducts (Mullerian ducts)
  • Develop from mesoderm until the end of the 8th week
  • Precursors to female internal sex organs
  • Differentiation is driven by estrogens and suppressed by MIF.

Mesonephric ducts (Wolffian ducts)

Clinical significance

The “default” sex in sexual development is female!

In the testes, Leydig cells Lead to male differentiation, and Sertoli cells Suppress female differentiation.

To remember the derivatives of the mesonephric duct in males, think “SEED”: S = Seminal vesicles, E = Epididymis, E = Ejaculatory duct, D = Ductus deferens!

References: [2][4][3]

External genitalia and urogenital differentiation

  • Description: development of the embryonic ducts into the external genitalia
  • Timeline: starts in week 9
  • Mechanism: primarily driven by the presence or absence of estradiol and dihydrotestosterone
    • Male: testosteronedihydrotestosterone (via 5α-reductase) → differentiation of embryonic structures into male external genitalia, bulbourethral glands, and prostate gland
    • Female: estradiol and absence of DHT → differentiation of embryonic structures into female external genitalia
Embryonic structure

Notable characteristics

Males

Development driven by DHT

Females

Development driven by estrogen

Genital tubercle

  • First forms primordial phallus

Urogenital sinus

  • Develops from cloaca during the 4–6th weeks
  • Precursor to bladder and urethra (both sexes

Urogenital folds

  • Ventral penile shaft
  • Penile urethra

Labioscrotal swelling

References: [3][2][5]

Descent of gonads

  • Description:
    • Migration of the testes caudally from their initial retroperitoneal location through the inguinal ring into the scrotum
    • Migration of the ovaries caudally to the pelvic rim
  • Timeline: complete by week 33 [3]
  • Mechanism
    • Descent of the testes
      1. The gubernaculum induces intra-abdominal migration.
      2. Increased intra-abdominal pressure supports the passage of testes through the inguinal canal.
      3. With the regression of the gubernaculum, the migration of the testes to the scrotum is complete.
Embryonic structure General description [6] Male remnant Female remnant Clinical significance
Gubernaculum
  • Fibrous tissue that aids in the descent of the gonads
  • Develops around week 7 and exists in males until descent of the testes into the scrotum is complete (typically ∼ 33 weeks)
  • Anchors testes within the scrotum (“scrotal ligament”)

Ovarian ligament

Processus vaginalis
  • Evagination of the peritoneum that accompanies the testis into the scrotum before closing
  • Obliterated

References: [3]