Development of the oesophagus

Origin

• The oesophagus develops from the foregut, just caudal to the primitive pharynx.
• Its lining epithelium and glands arise from endoderm.
• Its connective tissue, smooth muscle, and blood vessels are derived largely from surrounding splanchnic mesenchyme.
  The Developing Human: Clinically Oriented Embryology, p. 193.

Separation from the respiratory tract

• In week 4, a ventral laryngotracheal diverticulum develops from the foregut.
• Longitudinal tracheoesophageal ridges form and fuse to create the tracheoesophageal septum.
• This septum separates the foregut into:
  • A ventral laryngotracheal tube that forms the lower respiratory tract
  • A dorsal oesophagus

Elongation

• The early oesophagus is initially very short.
• It lengthens rapidly, mainly as the heart and lungs grow and move caudally.
• It reaches its final relative length by approximately the 7th week.
  The Developing Human: Clinically Oriented Embryology, p. 193.

Lumen and epithelial development

• Endodermal epithelial cells proliferate and may temporarily partly or completely occlude the oesophageal lumen.
• The lumen normally reopens by recanalization, completed by the end of the 8th week.

Muscular development

• Developmental evidence indicates that some smooth muscle in the upper oesophagus can transdifferentiate into striated muscle.
• Both muscle types receive motor innervation from the vagus nerves (CN X).

Clinical correlations

1. Oesophageal atresia with tracheo-oesophageal fistula
   • Usually results from abnormal posterior deviation of the tracheoesophageal septum and incomplete separation of trachea and oesophagus.
   • The commonest pattern is oesophageal atresia with a distal tracheo-oesophageal fistula.
   • It may cause polyhydramnios in pregnancy because swallowed amniotic fluid cannot reach and be absorbed by the fetal intestine.
   • After birth: excessive salivation, choking/coughing during feeds, regurgitation, and failure to pass a nasogastric tube.
2. Oesophageal stenosis or web
   • May result from incomplete recanalization during the 8th week.
   • It is often found in the distal third of the oesophagus.
3. Isolated oesophageal atresia
   • Can result from failure of oesophageal recanalization.

Development of the testis

1. Origin of the indifferent gonad

• The testes develop from the gonadal (genital) ridge, a thickening of coelomic epithelium on the medial side of the mesonephros, on the posterior abdominal wall.
• The gonadal ridge appears during the 5th week.
• Primordial germ cells originate in the epiblast, migrate via the wall of the yolk sac and dorsal mesentery of hindgut, and reach the gonadal ridge by approximately the 6th week.
• Until the 7th week, the gonad is morphologically indifferent and can develop as either a testis or ovary.

2. Genetic sex determination

• In a 46,XY embryo, expression of the SRY gene on the short arm of the Y chromosome initiates testicular differentiation at about week 7.
• SRY promotes SOX9 expression, leading to differentiation of supporting cells into Sertoli cells.
• Other genes supporting testicular development include WT1, SF1/NR5A1, FGF9, and DHH.

3. Formation of testis cords and tunica albuginea

• Surface epithelial cells proliferate and extend into the underlying mesenchyme, forming primitive sex cords.
• In the male, these cords persist in the medulla and form testis cords.
• Testis cords surround the primordial germ cells and later become seminiferous tubules at puberty.
• A dense fibrous layer, the tunica albuginea, develops beneath the surface epithelium. This separates the testis cords from the surface epithelium.
• Testis cords connect at the hilum of the testis with the rete testis.

4. Development of cells in the fetal testis

5. Hormonal actions and differentiation of genital ducts

Sertoli cells

• Fetal Sertoli cells secrete anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance.
• AMH causes regression of the paramesonephric (Müllerian) ducts, which otherwise form the uterine tubes, uterus, and upper vagina.

Leydig cells

• Leydig cells become evident around the 8th week and produce testosterone.
• Testosterone maintains and differentiates the mesonephric (Wolffian) ducts into:
  • Epididymis
  • Ductus deferens
  • Seminal vesicles
  • Ejaculatory ducts
• In peripheral tissues, testosterone is converted by 5-alpha-reductase to dihydrotestosterone (DHT).
• DHT forms the male external genitalia and prostate.

6. Connection with mesonephric ducts

• The rete testis connects with mesonephric tubules.
• Some mesonephric tubules persist as the efferent ductules.
• The mesonephric duct forms the epididymis, ductus deferens, seminal vesicle, and ejaculatory duct.

7. Descent of the testis

• The gubernaculum is a mesenchymal cord extending from the caudal pole of the testis toward the scrotal swelling. It guides descent.
• An evagination of peritoneum, the processus vaginalis, precedes the testis through the inguinal canal.
• The distal remnant of the processus vaginalis remains as the tunica vaginalis.
• The gubernaculum becomes the scrotal ligament, anchoring the testis to the scrotum.

Clinical correlations

• Cryptorchidism: failure of one or both testes to reach the scrotum. The testis may be abdominal, inguinal, or pre-scrotal.
• Indirect inguinal hernia: persistence of a patent processus vaginalis allows abdominal contents to enter the inguinal canal or scrotum.
• Hydrocele: fluid collection around the testis due to persistent communication with the peritoneal cavity or imbalance of fluid production and absorption.
• Swyer syndrome (46,XY gonadal dysgenesis): defective SRY-related testicular differentiation results in streak gonads and female internal genital structures.
• Androgen-insensitivity syndrome: testes and AMH are present, so Müllerian structures regress; however, androgen action is absent or reduced, impairing male external genital development.

Flowchart

Genital ridge + primordial germ cells
              ↓
Indifferent gonad
              ↓  SRY expression in 46,XY embryo
SOX9 activation and Sertoli-cell differentiation
              ↓
Testis cords + tunica albuginea + rete testis
              ↓
Sertoli cells → AMH → Müllerian-duct regression
Leydig cells → testosterone → Wolffian-duct differentiation
             → DHT → male external genitalia/prostate
             → INSL3 + testosterone → testicular descent