28-3 Spermatogenesis

Comparison of Mitosis and Meiosis in Reproduction

  • Background on Somatic Cells

    • Human somatic cells contain 23 pairs of chromosomes, totaling 46 chromosomes.

    • Each pair consists of one chromosome from the biological male and one from the biological female provided during fertilization.

    • Homologous Chromosomes: These are the two members of each of the 22 pairs that have similar sizes and genes.

    • Sex Chromosomes: The 23rd pair is heterologous, meaning they have different sizes and carry different genes.

  • Mitosis (Equational Division)

    • Mitosis is a part of somatic cell division resulting in two daughter cells.

    • Each daughter cell contains identical numbers and pairs of chromosomes as the parent cell.

    • Diploid (2n=462n = 46): Daughter cells are described as diploid because they contain both members of each chromosome pair.

  • Meiosis (Reductional and Equational Divisions)

    • Meiosis is a specialized cell division cycle that produces only gametes (sperm or oocytes).

    • It consists of two cycles: Meiosis I and Meiosis II.

    • The process results in four cells, each containing 23 individual chromosomes.

    • Haploid (n=23n = 23): These cells contain only one member of each homologous pair and one sex chromosome.

    • Fertilization Significance: Fusion of sperm and oocyte nuclei produces a cell with the normal diploid number of chromosomes rather than doubling it.

The Detailed Process of Meiosis

  • Preparation and DNA Replication

    • Just before meiosis begins, DNA replication occurs in the nucleus, similar to mitosis.

    • Chromosomes condense and become visible; each consists of two duplicate chromatids.

  • Meiosis I (Reductional Division)

    • Synapsis: The maternal and paternal chromosomes pair up. This involves 23 pairs where each member consists of two chromatids.

    • Tetrad: A matched set of four chromatids formed during synapsis.

    • Crossing Over: The exchange of genetic material between maternal and paternal chromatids, which increases genetic variation.

    • Prophase I: The nuclear envelope disappears toward the end of this stage.

    • Metaphase I: Tetrads line up along the metaphase plate.

    • Anaphase I: Tetrads break up. Maternal and paternal chromosomes separate and are randomly distributed to daughter cells. Unlike mitosis (where each cell gets a copy of every chromosome), in Meiosis I, each cell receives two copies of either the maternal or paternal chromosome.

    • Telophase I: Ends with the formation of two daughter cells, each containing unique combinations of chromosomes and totaling 23 chromosomes (n=23n = 23).

  • Meiosis II (Equational Division)

    • There is a brief interface between Meiosis I and II where no DNA replication occurs.

    • Stages include Prophase II, Metaphase II, Anaphase II, and Telophase II.

    • Anaphase II: The chromatids separate.

    • Telophase II: Yields four haploid cells, each containing 23 chromosomes.

    • Cytoplasmic Distribution: While chromosomes are evenly distributed, the cytoplasm may not be (e.g., in oogenesis).

Spermatogenesis and Male Gamete Production

  • Overview of Spermatogenesis

    • The process of sperm formation begins at puberty and can continue past age 70.

    • The entire process takes approximately 64 days.

    • Stages of development include:

      • Mitosis: Spermatogonia (stem cells) divide; one remains a spermatogonium, the other becomes a primary spermatocyte.

      • Meiosis I: Primary spermatocyte (2n2n) divides into two secondary spermatocytes (nn).

      • Meiosis II: Each secondary spermatocyte divides into two spermatids (nn).

      • Spermiogenesis: Physical maturation where four spermatids develop into four functional sperm.

  • Location and Progression

    • Occurs in the seminiferous tubules, starting from the outermost layer and moving toward the lumen.

    • Cells move closer to the lumen at each developmental step.

  • Cytoplasmic Bridges and Spermiation

    • Spermatids remain interconnected by bridges of cytoplasm because cytokinesis is incomplete in meiosis.

    • Bridges allow for the transfer of nutrients and hormones to ensure synchronized development.

    • Spermiation: The stage where a sperm loses its attachment to the nurse cell and enters the lumen of the tubule.

The Role and Function of Nurse Cells (Sertoli Cells)

  • General Role

    • Nurse cells surround and support developing spermatocytes and spermatids.

    • They provide a specialized microenvironment for spermatogenesis.

  • Five Major Functions

    1. Maintenance of the Blood-Testis Barrier: Tight junctions between nurse cells isolate the tubule from general circulation. It separates the basal compartment (spermatogonia) from the luminal compartment (meiosis/spermiogenesis). This protects sperm from immune attack (sperm-specific antigens are otherwise seen as foreign).

    2. Support of Mitosis and Meiosis: Stimulated by Follicle Stimulating Hormone (FSH) and testosterone to promote division.

    3. Support of Spermiogenesis: They enfold spermatids, providing nutrients and chemical stimuli. They also phagocytize cytoplasm shed by developing spermatids.

    4. Secretion of Inhibin: A peptide hormone that provides negative feedback by depressing pituitary production of FSH and hypothalamic GnRH.

    5. Secretion of Androgen-Binding Protein (ABP): Stimulated by FSH, ABP binds androgens (testosterone) in the luminal fluid to increase concentration and stimulate spermiogenesis.

Anatomy and Maturation of Sperm

  • Functional Maturation

    • Sperm in the lumen are physically mature but functionally immature (immobile).

    • Epididymis: Sperm pass through for up to two weeks to complete functional maturation.

    • Capacitation: Process to become motile and functional.

      1. Step 1: Become motile when mixed with seminal gland secretions.

      2. Step 2: Become capable of fertilization when exposed to the female reproductive tract.

  • Physical Structure

    • Head: Flattened ellipse containing the nucleus and densely packed chromosomes.

    • Acrosome: A membranous compartment at the tip containing enzymes required for fertilization; formed from the Golgi apparatus.

    • Neck: Contains both centrioles from the original spermatid.

    • Middle Piece: Contains mitochondria arranged in a spiral to provide ATP for movement.

    • Tail: The only flagellum in the human body; moves with a corkscrew motion (different from the wave-like beat of cilia).

    • Organelle Loss: Lacks ER, Golgi, lysosomes, and peroxisomes to reduce mass and size for mobility. Nutrients (fructose) are absorbed from surrounding fluid.

Hormonal Regulation of Male Reproduction

  • Hypothalamic-Pituitary-Testicular Axis

    • GnRH (Gonadotropin-Releasing Hormone): Released by the hypothalamus in pulses every 60 to 90 minutes. It travels via the hypophyseal portal system.

    • FSH (Follicle-Stimulating Hormone): Released by the anterior pituitary; targets nurse cells to promote spermatogenesis and ABP production.

    • LH (Luteinizing Hormone): Released by the anterior pituitary; targets interstitial endocrine cells to release testosterone.

  • Testosterone Transport and Action

    • Gonadal Steroid-Binding Globulin (GBG): Carries approximately two-thirds of circulating testosterone.

    • Albumin: Binds the remaining one-third.

    • Mechanism: Diffuses across target cell membranes, binds to intracellular receptors, and then to nuclear DNA.

  • Dihydrotestosterone (DHT) and Estradiol

    • DHT: Converted from testosterone; levels are about 10% of circulating testosterone. External genitalia and the prostate are highly sensitive to DHT.

    • Estradiol: Adult males have small amounts (2 ng/dL2\,ng/dL vs 525 ng/dL525\,ng/dL for testosterone). 70% is formed from testosterone via the enzyme aromatase.

Questions & Discussion

  • Q: What is the name of the cell at each stage of sperm development, from mitosis to spermatogenesis?

    • A: During mitosis, the spermatogonium divides into another spermatogonium and a primary spermatocyte. During meiosis I, the primary spermatocyte divides into two secondary spermatocytes. During meiosis II, each secondary spermatocyte divides into two spermatids. During spermiogenesis, spermatids develop into sperm.

  • Q: In which of the four parts of a sperm are the centrioles found?

    • A: The centrioles are found in the neck of the sperm.

  • Q: What effect would a low FSH level have on sperm production?

    • A: Low FSH levels would lead to low levels of testosterone in the seminiferous tubules, decreasing both the sperm production rate and sperm count.

Clinical Considerations and Pathologies

  • DHEA (Dehydroepiandrosterone)

    • Primary androgen from the adrenal cortex (zona reticularis). Banned by the Olympic Committee. High levels in females are linked to ovarian cancer.

  • Benign Prostatic Hyperplasia (BPH)

    • Enlargement of the prostate common in men over age 50. Tied to declining testosterone and rising estrogens. Can cause prostatic concretions and block the urethra. Treated via TURP (Transurethral Prostatectomy).

  • Prostate Cancer

    • Risk increases with age and family history. Linked to high DHT levels. Drugs like Finasteride and Dutasteride block DHT conversion to lower risk.

    • PSA (Prostate Specific Antigen): A blood test used to screen for prostate cancer; elevated levels indicate potential malignancy.