Spermatogenesis and Male Hypothalamic-Pituitary-Gonadal Axis

Objectives

• Understand the three phases of spermatogenesis.

• Comprehend the male hypothalamic-pituitary-gonadal axis and its control over reproductive functions.

Three Phases of Spermatogenesis

• Spermatogenesis: Process of producing mature sperm cells involving three distinct phases:

  1. Mitotic Proliferation

  2. Meiotic Division

  3. Spermiogenesis

Spermatogenic Cells

• Spermatogonium (2n): Stem cell; undergoes mitosis to produce daughter cells.

• Primary Spermatocyte (2n): Begins the meiotic process.

• Secondary Spermatocyte (n): Result of Meiosis I.

• Spermatids (n): Developed from secondary spermatocytes during Meiosis II.

• Spermatozoa (n): Final mature sperm cell.

Phase 1: Mitotic Proliferation

• Daughter cells from spermatogonia:

  • One remains as a precursor (germ cell line).

  • The other moves towards the lumen and differentiates into primary spermatocytes.

• Begins with the production of 2 spermatogonia (diploid).

Phase 2: Meiotic Division

• Meiosis I: Two secondary spermatocytes (haploid) are produced.

• Meiosis II: Each secondary spermatocyte forms 2 spermatids, resulting in a total of 4 spermatids, with chromosomal distribution being:

  • 2 with an X chromosome

  • 2 with Y chromosomes

Phase 3: Spermiogenesis

• Transformation from spermatids to spermatozoa:

  • Cells elongate and develop flagella.

  • Involves cytoplasmic reduction and differentiation of the tail.

• Spermiation: Release of sperm from Sertoli cells.

• Total time for transformation: ~74 days from spermatogonia to functional spermatozoa.

• Normal sperm production rate: Approximately 300 million sperm daily, decreasing with age.

Male Hypothalamic-Pituitary-Gonadal Axis

• Functions:

  1. Androgen (testosterone) biosynthesis and release by Leydig cells in the testes.

  2. Regulation of spermatogenesis in seminiferous tubules.

Key Hormones

• GnRH (Gonadotropin-Releasing Hormone): Released by hypothalamus and stimulates anterior pituitary to secrete FSH and LH.

• LH (Luteinizing Hormone): Stimulates Leydig cells to produce testosterone.

• FSH (Follicle Stimulating Hormone): Promotes spermatogenesis and supports Sertoli cell function.

GnRH Mechanism

• Release: Pulsatile nature with 8-14 pulses per day, influencing LH and FSH simultaneously but with different amplitudes.

• Inhibition: Continuous high doses of GnRH can suppress LH and FSH release, leading to decreased testosterone production (chemical castration potential).

Mechanisms of LH on Spermatogenesis

• Action: Binds to G-protein-coupled receptors in Leydig cells, activating gene transcription and increasing testosterone synthesis.

• Feedback: Testosterone modulates both LH secretions from the pituitary and GnRH release from the hypothalamus via a negative feedback loop.

Mechanisms of FSH on Spermatogenesis

• Action: Binds to G-protein-coupled receptors in Sertoli cells, enhancing protein synthesis, particularly Androgen-binding protein (ABP) which maintains testosterone levels.

• Growth Factors: Increases expression of various growth factors fostering sperm cell development.

• Inhibins: Produced by Sertoli cells as negative feedback for FSH secretion by the pituitary.