Gametogenesis: Spermatogenesis and Oogenesis

Gametogenesis

Dr. Shahid Bakhsh Rangrej, MD Anatomy, Saint James School of Medicine.

Learning Objectives

• Define gametogenesis.

• Explain spermatogenesis and oogenesis.

• Compare key differences between spermatogenesis and oogenesis.

Definition of Gametogenesis

• Gametogenesis is the biological process involving the formation and maturation of germ cells, known as GAMETES (spermatozoa in males and ova in females).

• It is broadly classified into two main types:

  • Spermatogenesis: The process in males.

  • Oogenesis: The process in females.

Cell Division: Mitosis and Meiosis

• Cell division is a fundamental part of the larger cell cycle in eukaryotes.

• There are two distinct types of cell division:

  • MITOSIS:

    • A vegetative division, meaning it produces somatic cells.

    • Each daughter cell is genetically identical to the parent cell.

    • The chromosome number remains the same (e.g., $2n$ to $2n$).

  • MEIOSIS:

    • A reductive cell division.

    • Produces haploid gametes (sperm and ova).

    • The chromosome number is halved (e.g., $2n$ to $n$).

    • Involves two successive divisions: Meiosis I and Meiosis II.

Stages of Meiosis Illustrated

• Parent Cell (before chromosome duplication): Diploid, e.g., $2n=4$ chromosomes.

• Chromosome Duplication: Chromosomes duplicate to form duplicated chromosomes (two sister chromatids).

• MEIOSIS I:

  • Prophase I: Homologous chromosomes undergo synapsis, forming tetrads. Crossing over occurs, leading to genetic recombination. This stage is particularly long in oogenesis, with an arrest phase.

  • Metaphase I: Tetrads align at the metaphase plate.

  • Anaphase I: Homologous chromosomes separate and move to opposite poles; sister chromatids remain attached.

  • Telophase I: The cell divides, resulting in two haploid daughter cells ($n$ chromosomes, each still with two chromatids).

• MEIOSIS II:

  • (No further chromosomal duplication occurs between Meiosis I and II).

  • Prophase II

  • Metaphase II: Chromosomes (each with two chromatids) align at the metaphase plate.

  • Anaphase II: Sister chromatids separate and move to opposite poles.

  • Telophase II: The cells divide, resulting in a total of four haploid daughter cells ($n$ chromosomes, each with one chromatid).

Nondisjunction

• Proper disjunction: Correct separation of chromosomes or chromatids.

• Nondisjunction: Failure of homologous chromosomes to separate during Anaphase I or sister chromatids to separate during Anaphase II.

• Consequences of nondisjunction include chromosomal disorders such as Down syndrome (Trisomy 21), Turner syndrome (Monosomy X), and Klinefelter syndrome (XXY).

Spermatogenesis

• Definition: The process by which spermatogonia (diploid primordial germ cells) develop into mature sperms (spermatozoa).

• Location: Occurs within the seminiferous tubules of the testes.

• Timing: Starts at puberty and usually continues uninterrupted throughout a male's life until death.

Stages of Spermatogenesis

1. Proliferation (Mitosis):

   • Spermatogonia A (diploid, $2n$) undergo mitotic divisions to produce more spermatogonia A, ensuring a continuous supply of germ cells. This stage takes approximately $16$ days.

   • They also differentiate into Spermatogonia B (diploid, $2n$).

2. Growth (Meiosis I):

   • Spermatogonia B enlarge and become Primary Spermatocytes (diploid, $2n$).

   • Primary Spermatocytes enter Meiosis I, a process that takes approximately $24$ days.

   • Meiosis I results in two Secondary Spermatocytes (haploid, $n$), each with $23$ chromosomes, each chromosome consisting of two chromatids.

3. Maturation (Meiosis II):

   • Secondary Spermatocytes rapidly undergo Meiosis II (within some hours).

   • Meiosis II results in two Spermatids (haploid, $n$) from each secondary spermatocyte, leading to a total of four spermatids from one primary spermatocyte. Each spermatid has $23$ chromosomes, each consisting of a single chromatid.

4. Transformation (Spermiogenesis):

   • Spermatids undergo a process of morphological change called spermiogenesis to become fully formed Spermatozoa (mature sperms).

   • This involves significant structural changes like the formation of the head (containing the nucleus), midpiece (containing mitochondria), and tail (flagellum).

Post-Formation Maturation

• Fully formed spermatozoa enter the lumen of the seminiferous tubules.

• They then migrate to the epididymis, where they acquire functional maturity and motility.

Clinical Relevance – Spermatogenesis (Male Infertility)

• Oligospermia: Low sperm count (<15 million/mL).

• Azoospermia: No sperm present in the ejaculate.

• Asthenozoospermia: Poor sperm motility.

• Teratozoospermia: Abnormal sperm morphology.

• Causes: Can be multifactorial, including hormonal imbalances, varicocele (enlargement of veins within the scrotum), genetic factors, and exposure to toxins.

• Consequence: Male infertility.

Oogenesis

• Definition: The process by which oogonia (primordial germ cells) differentiate into mature oocytes (ova).

• Yield: Oogenesis yields a single haploid definitive oocyte and three small, non-functional, haploid polar bodies.

• Timing: Begins prenatally (before birth) and is completed after puberty, continuing until menopause.

Stages of Oogenesis

Before Birth (Embryonic and Fetal Period)

1. Oogonia Migration and Mitosis:

   • During early fetal development, primordial germ cells called oogonia migrate from the embryonic yolk sac into the ovarian cortex.

   • They multiply by mitotic divisions, producing diploid ($46$ chromosomes) oogonia.

2. Primary Oocyte Formation and Meiotic Arrest:

   • By the $4^{th}$ and $5^{th}$ months of human fetal development, some oogonia enlarge and assume the potential to develop into mature gametes.

   • At this stage, they become known as Primary Oocytes and commence the first stage of meiotic division (Meiosis I).

   • By the $7^{th}$ month of fetal development, primary oocytes become encapsulated by a single layer of flattened follicular cells of epithelial origin, forming primordial follicles.

   • Follicular cells produce an oocyte maturation inhibitor, which prevents the early completion of meiotic prophase of the primary oocyte.

   • This encapsulation arrests the first meiotic division at the diplotene stage of Prophase I.

Childhood

• The ovary remains inactive, housing primordial follicles. Some atresia (degeneration) of primordial follicles occurs during this period.

Monthly, from Puberty to Menopause

1. Follicle Maturation:

   • Every month, approximately $20$ primordial follicles mature into primary follicles.

   • Some primary follicles further mature into secondary (antral) follicles.

   • Primary follicles that do not mature undergo atresia.

2. Meiosis I Completion and Secondary Oocyte Formation:

   • Typically, only one secondary follicle matures into a vesicular (Graafian) follicle.

   • Within the vesicular follicle, the primary oocyte completes the first meiotic division just before ovulation.

   • This completion yields two haploid ($23$ chromosomes) cells:

     • A Secondary Oocyte: A large cell containing most of the cytoplasm and nutrient reserves.

     • The First Polar Body: A small, non-functional cell that degenerates.

   • The secondary oocyte is immediately arrested in the second meiotic metaphase.

3. Ovulation:

   • The vesicular follicle ruptures, releasing the secondary oocyte (arrested in Metaphase II).

4. Meiosis II Completion (If Fertilization Occurs):

   • If the secondary oocyte is fertilized by a sperm, it rapidly completes the second meiotic division.

   • This completion yields:

     • An Ovum (definitive oocyte): The mature female gamete.

     • The Second Polar Body: Another small, non-functional cell that degenerates.

5. Corpus Luteum and Corpus Albicans:

   • After ovulation, the ruptured follicle transforms into the Corpus Luteum, which produces hormones like progesterone and estrogen.

   • If pregnancy does not occur, the corpus luteum degenerates into the Corpus Albicans.

Follicle Development Stages

• Primordial Follicle: Most numerous. Primary oocyte enveloped by one layer of flattened follicular cells.

• Growing Follicles:

  • Early Primary Follicle: Follicular cells become cuboidal.

  • Late Primary Follicle: Multiple layers of follicular cells, Zona Pellucida appears.

  • Secondary (Antral) Follicle: Characterized by the formation of an antral cavity within the granulosa cell layers.

• Graafian Follicle: A mature vesicular follicle, containing a primary oocyte (prior to Meiosis I completion) or secondary oocyte (after Meiosis I completion, before ovulation).

• Ruptured Follicle: At the time of ovulation, releasing the secondary oocyte.

• Corpus Luteum: Former follicle cells after ovulation, producing hormones.

• Corpus Albicans: Degenerated corpus luteum, appearing as a scar.

Hypothalamic-Pituitary-Ovarian Axis

• This axis regulates female reproductive function through a complex interplay of hormones.

• Hypothalamus releases GnRH (Gonadotropin-Releasing Hormone).

• Anterior Pituitary responds to GnRH by releasing FSH (Follicle-stimulating Hormone) and LH (Luteinizing Hormone).

• Ovary responds to FSH and LH:

  • Granulosa cells produce Estrogens (under FSH and LH influence) and Inhibin (which inhibits FSH) and Activin.

  • Theca cells produce Androgens which are then converted to estrogens by granulosa cells.

  • Progestins are produced primarily by the Corpus Luteum.

• Estrogens and Progestins exert feedback on the hypothalamus and pituitary, and also act on target tissues, influencing behavioral effects and reproductive cycles.

Key Differences Between Spermatogenesis and Oogenesis

Clinical Application Questions

Question 1: A biopsy of testes shows spermatids that fail to transform into mature spermatozoa. Which process is defective?

• Correct Answer: A) Spermiogenesis

  • Explanation: Spermiogenesis is the specific transformation of spermatids into mature, morphologically distinct spermatozoa, involving the loss of cytoplasm and formation of a flagellum and acrosome.

Question 2: A $32$-year-old woman undergoes ovarian stimulation for in vitro fertilization. At the time of oocyte retrieval, the secondary oocytes are aspirated from the ovarian follicles. At this stage, the oocytes have completed meiosis I but remain arrested until fertilization occurs. In which of the following stages are these oocytes arrested?

• Correct Answer: D) Metaphase II

  • Explanation: Primary oocytes are arrested in Prophase I until puberty. After Meiosis I is completed, just before ovulation, the secondary oocyte is formed and immediately arrests in Metaphase II, awaiting fertilization. If fertilization occurs, it completes Meiosis II. If no fertilization, it degenerates.