Gametogenesis and Reproductive System

Gametogenesis

• The process of producing gametes
• Spermatogenesis is the production of sperm in males
• Oogenesis is the production of oocytes in females

Male Reproductive System

• Consists of:
  • Paired testes
  • Genital ducts
  • Accessory genital glands, including seminal vesicles, prostate gland, and bulbourethral glands
  • Penis

Testes

• Glands where sperm and testosterone are produced
• Composed of ~300 internal compartments called testicular lobules
• Each lobule contains 1-4 seminiferous tubules where sperm are produced
• Located outside the body to maintain a lower temperature required for sperm development

Seminiferous Tubules

• Sperm produced at a rate of about 20 million per day in a young adult
• Range from 30-70 cm in length and 150-250 μm in diameter
• Lined by a thick complex epithelium known as the seminiferous or germinal epithelium
• This epithelium consists of 4 to 8 cell layers and contains spermatogenic cells and Sertoli cells

Leydig Cells

• During puberty, they develop as large round or polygonal cells with central nuclei and eosinophilic cytoplasm
• Possess numerous mitochondria, a well-developed Golgi complex, and many lipid droplets

Leydig Cells and Testosterone

• Lipid droplets contain cholesterol esters, which are precursors of testosterone
• Testosterone secretion is triggered by pituitary gonadotropin, luteinizing hormone (LH), also called interstitial cell stimulating hormone (ICSH)

Sertoli Cells

• Large, nondividing cells
• Physically and metabolically support developing sperm cell precursors

Stages of Sperm Production

• Involves three main stages:
  • Spermatogenesis: Formation of spermatids from spermatogonium cells
  • Spermiogenesis: Formation of sperm from spermatids
  • Spermiation: Release of mature sperms into the seminiferous tubule
• The entire process spans nearly 2 months (64 days)

Spermatogenesis

• The process takes place in the lumen of the seminiferous tubules
• As sperm cells go through the lumen, they mature

Spermatogonia

• Begins at puberty with the proliferation of stem and progenitor cells
• These are small, round cells approximately 12 μm in diameter
• Located in a basal niche of the epithelial wall of the tubules, close to the basement membrane and are closely associated with Sertoli cells

Types of Spermatogonia

• Type Ad (Dark type A cells): Stem cells with dark, ovoid nuclei
• Divide to produce new stem cells (Type Ad) and Type Ap cells
• Type Ap (Pale type A cells): Possess more pale-staining ovoid nuclei, which divide more rapidly as transit amplifying (progenitor) cells

Key Characteristics of Additional Spermatogonia Types

• Pale type A spermatogonia have a pale-staining nucleus, spherical mitochondria, a small Golgi complex, and abundant free ribosomes
• Type B spermatogonia undergo mitosis and give rise to primary spermatocytes
• Dark type A spermatogonia act as reserve cells with dark nuclei
• Have the potential to produce pale type A cells
• Mitotically active; give rise either to more cells of same type or to type B spermatogonia (the starting point for spermatocytes)

Primary Spermatocytes

• Undergo meiosis
• Meiosis includes two divisions
• The first division is meiotic (meiosis I)

Secondary Spermatocytes

• Two haploid cells are produced as a result of the first meiotic division
• Both undergo a second division that is mitotic (meiosis II)
• Four haploid spermatids are produced by each primary spermatocyte

Chromosome Composition

• Two spermatids contain 22 autosomes and one X chromosome (22 + X, 22 + X)
• Two spermatids contain 22 autosomes and one Y chromosome (22 + Y, 22 + Y)

Spermiogenesis

• Formation and differentiation process of sperm cells from spermatids that results in sperm with a special morphologic appearance
• Includes maturation and differentiation events
• Three stages:
  • Acrosome development
  • Tail development
  • Nuclear condensation

Spermiogenesis and Spermatozoon Formation

• The spermatid is transformed into the spermatozoon

Three Step Transformation

• Nuclear material (chromatin) condenses, and the nucleus moves towards one pole of the cell to form the head of the spermatozoon
• The Golgi apparatus forms the acrosomal cap covering the anterior two-thirds of the nucleus
• The centrosome divides into two centrioles

Final Steps of Spermiogenesis

• One centriole (distal) becomes spherical and moves to the posterior end of the nucleus to occupy the neck region, giving rise to the axial filament
• The other centriole (proximal) moves away from the first centriole and becomes ring-shaped and forms the annulus/ring around the distal end of the middle piece through which the axial filament passes

Additional Final Steps of Spermiogenesis

• The part of the axial filament between the neck and annulus becomes surrounded by mitochondria, forming the middle piece
• The remaining part of the axial filament elongates to form the tail

Spermiation

• Most of the cytoplasm of the spermatid is shed off, but the cell membrane remains
• The cell membrane covers the entire spermatozoon
• After spermiogenesis, sperm heads become embedded in Sertoli cells
• Mature sperm are released from the seminiferous tubules through spermiation

Sperm Anatomy

• Mature sperm consists of a head, a midpiece, and a tail

Sperm Structures

• The head contains the nucleus with tightly packed chromatin fibres
• The acrosome on top of the head contains enzymes for penetrating and entering the oocyte
• The midpiece has a central filamentous core with many mitochondria surrounding it, used for ATP production
• The tail provides the movements to go and penetrate the oocyte

Male Infertility Factors

• 15% of couples experience infertility (inability to conceive)
• Male factors account for 40% of these cases and include:
  • Decreased sperm parameters
  • Low concentration
  • Low motility
  • Low normal morphology
  • Azoospermia
  • DNA fragmentation
  • High ROS levels
  • Unknown reasons

Sperm Parameters

• Oligozoospermia: Low sperm concentration (<20 million/ml)
• Astenozoospermia: Low motility rate (<50% total motility; <15% progressive motility)
• Teratozoospermia: Low morphology rate (<4% normal morphology rate)
• OAT (Oligoastenoteratozoospermia): All of the parameters are abnormal