Spermatogenesis, Functions of Sertoli Cells, and Structure of Sperm

INTRODUCTION

PART 1: SPERMATOGENESIS

Site

• Seminiferous tubules of the testes (constitute ~80% of testicular volume)
• Stimulated by FSH (from anterior pituitary) and testosterone (from Leydig cells)
• Begins at puberty (~13 years) and continues lifelong, decreasing in old age

Duration

• Full cycle takes approximately 64-74 days in humans
• ~128 million sperm are produced daily (2 million spermatogonia begin the process daily; each yields 64 spermatozoa)

STAGES OF SPERMATOGENESIS

Phase 1: Mitotic Phase (Proliferation of Spermatogonia)

• Spermatogonia are the stem cells lying on the basal lamina of the seminiferous tubules
• They undergo repeated mitotic divisions to maintain the stem cell pool and produce daughter cells committed to differentiation
• Type A spermatogonia - dark (reserve stem cells) and pale (actively dividing)
• Type B spermatogonia - give rise to primary spermatocytes
• These cells remain connected by cytoplasmic bridges throughout differentiation, ensuring synchronized development

Phase 2: Meiotic Phase (Reduction Division)

• Type B spermatogonia enlarge and undergo DNA replication to become primary spermatocytes (the largest germ cells in the seminiferous tubule; 46 chromosomes, 4N DNA)
• They cross the blood-testis barrier into the adluminal compartment

• Each primary spermatocyte undergoes Meiosis I (reductive division)
• This produces two secondary spermatocytes (haploid - 23 chromosomes each, 2N DNA)
• Secondary spermatocytes are approximately half the size of primary spermatocytes

• Each secondary spermatocyte undergoes Meiosis II (equatorial division)
• This produces two spermatids per secondary spermatocyte
• Total = 4 haploid spermatids from each primary spermatocyte (23 chromosomes, 1N DNA)

Phase 3: Spermiogenesis (Spermatid to Spermatozoon Transformation)

Spermatozoa leaving the testis are not yet motile. They acquire full motility and fertilizing capacity during passage through the epididymis - a process called capacitation (completed in the female reproductive tract).

HORMONAL REGULATION OF SPERMATOGENESIS

PART 2: FUNCTIONS OF SERTOLI CELLS

1. Support and Nutrition of Developing Germ Cells

• Spermatids are isolated from the bloodstream and cannot absorb nutrients directly
• Sertoli cells provide nutrients, metabolic substrates (lactate, pyruvate), and growth factors to developing germ cells throughout their maturation
• Spermatids mature embedded in deep folds of Sertoli cell cytoplasm

2. Blood-Testis Barrier (BTB)

• Adjacent Sertoli cells form tight junctions (zonula occludens) with each other
• This creates the blood-testis barrier, dividing the seminiferous epithelium into:
  • Basal compartment - contains spermatogonia and early primary spermatocytes (exposed to blood)
  • Adluminal (luminal) compartment - contains meiotic and post-meiotic cells (protected)
• Functions of BTB:
  • Prevents autoimmune attack against haploid germ cell antigens
  • Maintains the unique ionic environment needed for spermatogenesis
  • Protects developing sperm from bloodborne toxins and drugs

3. Secretion of Androgen-Binding Protein (ABP)

• Sertoli cells secrete ABP (stimulated by FSH and testosterone)
• ABP binds and concentrates testosterone within the lumen of the seminiferous tubule
• Maintains high local testosterone concentrations essential for spermatid maturation

4. Secretion of Inhibin

• Sertoli cells secrete inhibin (a glycoprotein hormone)
• Inhibin exerts negative feedback on FSH secretion from the anterior pituitary
• This is the key endocrine feedback loop controlling spermatogenesis rate

5. Secretion of Tubular Fluid

• Sertoli cells secrete an aqueous fluid into the seminiferous tubule lumen
• This fluid transports sperm from the tubule toward the epididymis
• The fluid has a specific composition: rich in androgens, estrogens, K⁺, inositol, glutamic acid

6. Secretion of Mullerian Inhibiting Substance (MIS / AMH)

• Also called Anti-Mullerian Hormone (AMH)
• Secreted during fetal development to cause regression of the Mullerian (paramesonephric) ducts
• This ensures male differentiation of the reproductive tract

7. Phagocytosis of Residual Bodies

• During spermiogenesis, excess cytoplasm is shed as residual bodies
• Sertoli cells phagocytose and digest these residual bodies

8. Aromatase Activity (Estrogen Production)

• Sertoli cells contain aromatase (CYP19)
• They convert androgens to estrogens
• The rete testis fluid is rich in estrogen, which promotes fluid reabsorption and sperm concentration

9. Additional Secretions

• Transferrin - transports iron to developing sperm
• Ceruloplasmin - copper-transporting protein
• Plasminogen activator - converts plasminogen to plasmin (involved in remodeling)
• GDNF (Glial cell line-derived neurotrophic factor) - regulates spermatogonial self-renewal
• SCF (Stem cell factor) - supports germ cell survival

PART 3: DIAGRAM OF SPERM (SPERMATOZOON)

Labeled Diagram Description (for drawing in exam):

                    ACROSOME (cap)
                  ┌──────────────┐
                  │  NUCLEUS     │  ← HEAD (~4.5 μm)
                  │  (condensed  │
                  │  chromatin)  │
                  └──────┬───────┘
                         │ NECK (connecting piece + proximal centriole)
                  ═══════╪══════════ ← MIDDLE PIECE (~5-7 μm)
                  ║ MITOCHONDRIAL SHEATH ║
                  ║ (helical, around axoneme) ║
                  ═══════╪══════════ ← ANNULUS
                         │
                  ───────┼─────────── PRINCIPAL PIECE (~50 μm)
                  (fibrous sheath + axoneme + outer dense fibers)
                         │
                  ───────┼─────────── END PIECE (~5 μm)
                         ▼           (axoneme only, no sheath)

Parts of Sperm and Their Functions:

SUMMARY TABLE