Meiosis

Overview of Meiosis

• Meiosis: a cellular division process that creates aneuploid gametes in sexually reproducing species
• Occurs in ovaries and testes
• Prior to mitosis, the cell undergoes a growth and DNA replication cycle called interphase.
• 1 round of DNA replication (interphase), followed by 2 rounds of cellular division
• 2 rounds of cell division (meiosis I and meiosis II) divided into phases:
  • Prophase
  • Metaphase
  • Anaphase
  • Telophase
  • Cytokinesis
• The resulting daughter cells have ½ the number of chromosomes as the mother cells.
• Nomenclature: n = number of homologous chromosomes, c = total number of chromosomes (homologous and sister)

Meiosis I

Following DNA replication, meiosis I creates 2 daughter cells containing half the genetic information of the mother cell (1n) but the same number of chromosomes (2c) by segregating sister chromatids into the same daughter cell.

• Prophase I: longest phase of meiosis
  • Chromosomes start to condense.
  • Homologous chromosomes align and a synapse forms.
  • Crossing over (overlap and fusion of homologous areas of aligned chromosomes, causing an exchange of genetic material) occurs and is visible because of the chiasmata (point of crossing over).
  • Crossing over occurs between sister chromatid segments (homologous recombination).
  • Homologous chromosomes separate as the chromosomes become fully condensed.
• Metaphase I
  • The nuclear membrane disassembles.
  • Chromosomes align themselves on the equatorial plane and attach to spindle fibers.
  • Spindle fibers push the chromosome pairs to stay in the middle of the cell.
  • Cohesins hold sister chromatids together from replication to anaphase.
• Anaphase I
  • Spindle fibers shorten.
  • Separation of the chromosome pairs
  • The cell becomes oblong in preparation for division.
• Telophase I and cytokinesis
  • Spindle fibers disassemble.
  • Chromosomes become less condensed, and the nuclear envelope may start to re-form.
  • Cytokinesis divides the cell into 2 daughter cells, each of which contains only 1 set of chromosomes and is considered haploid.

Meiosis II

Meiosis II is a cellular division event wherein the number of chromosomes in the daughter cells is halved from that of the mother cell.

• Meiosis II: similar to meiosis I but not preceded by interphase (DNA replication)
• Stages of meiosis II:
  • Prophase II
    • The nuclear envelope disassembles.
    • Spindle fibers again form and chromosomes start to condense.
  • Metaphase II
    • Spindle fibers push the chromosomes to the middle of the cell.
    • The cell elongates.
  •  Anaphase II
    • Spindle fibers shorten.
    • Sister chromatids are separated.
  • Telophase II
    • Chromosomes become less condense.
    • Spindle fibers disassemble.
    • Cytokinesis: Cells divide into 2 daughter cells that are haploid.

Meiosis in Humans

The human karyotype normally contains 23 pairs of chromosomes.

• 22 pairs of autosomes
• 1 pair of allosomes (sex chromosomes)
• 23 chromosomes from each parent
• Total of 46 chromosomes

Meiosis is important in the production of haploid cells (gametes).

• Spermatocytes and oocytes are the 2 types of haploid cells (gametes) produced during meiosis.
• Sexual reproduction: 2 haploid cells combine to make 1 diploid cell.
• 1 haploid from the mother, 1 haploid from the father
• Spermatocytes are produced during spermatogenesis.
• Oocytes are produced during oogenesis.

Spermatogenesis

• Occurs in the seminiferous tubules of the testes
• Spermatogonial stage
  • Mitotic clonal expansion occurs.
  • Spermatogonia = precursor cells for spermatocytes
  • Type A spermatogonia from the primordial germ cell divide to maintain the stem cell pool population.
  • Some of the type A spermatogonia return or stay at the resting pool while some proliferate and undergo differentiation.
  • Type A spermatogonia may be converted to type B spermatogonia.
  • Type B spermatogonia then enter the preleptotene stage and become primary spermatocytes.
• Meiotic stage
  • Primary spermatocytes undergo 2 stages of meiosis.
  • Haploid daughter cells are called round spermatids.
• Spermiogenesis stage
  • Round spermatids enter the spermatogenesis stage.
  • Spermatids undergo nuclear and cytoplasmic changes, leading to the formation of spermatozoa:
    • Formation of the acrosome (a modified lysosome)
    • The nucleus becomes condensed and is moved to the periphery of the cell.
    • Microtubules then form, producing flagella.
    • A large part of the cytoplasm is removed as a residual body.
    • Sertoli cells phagocytose these bodies.
  • Spermatozoa are stored to mature before being released into the epididymis.

Oogenesis

• Birth to puberty
  • Before birth, oogonium, which also arise from germs cells, undergo mitosis to produce primary oocytes.
  • Undergoes meiosis I, but process is halted at the prophase I
• After puberty
  • Primary oocytes complete meiosis I forming a secondary oocyte and the 1st polar body
  • The secondary oocytes then begin meiosis II and are ovulated.
  • The secondary oocyte are arrested in metaphase II.
• Fertilization 
  • A secondary oocyte and a sperm cell fuse.
  • Meiosis II proceeds and is completed when the sperm cell completely penetrates the secondary oocyte.
  • A 2nd polar body and the ovum are produced after meiosis II.
  • When the nuclei of the sperm cells and the ovum unite, a diploid zygote is produced.

Meiosis vs. Mitosis

• The major difference between these 2 processes is the number of steps needed to complete cell division.
• Mitosis involves a single division producing 2 daughter cells similar to the parent cell.
• Meiosis occurs as a 2-cell division process that produces 4 daughter cells that are completely distinct from both each other and the parent cells.
• The final product of meiosis has half the number of chromosomes compared to the parent cell, while mitosis produces daughter cells with the same number of chromosomes.
• Mitosis occurs in somatic cells and during early cell division in gamete formation, while meiosis occurs only at the final division of gamete maturation.

Clinical Relevance

• Down syndrome ((DS) trisomy 21): the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Down syndrome results from a failure of meiosis. Characteristic traits include upslanting, almond-shaped eyes with skin covering the inner aspects, a broad flattened nasal bridge, small rounded ears, and a small mouth with a large tongue. 
• Patau’s syndrome (trisomy 13): a genetic syndrome caused by the presence of 3 copies of chromosome 13. Findings include craniofacial and cardiac malformations, severe intellectual disability, and greatly reduced life expectancy. Most infants do not survive past 3 months. 
• Edwards syndrome (trisomy 18): a genetic syndrome caused by the presence of an extra chromosome 18, which can be from 3 full copies of chromosome 18 or an additional segment of chromosome 18. Noted abnormalities include intrauterine growth retardation, overlapping fingers, typical craniofacial features, rocker bottom feet, and congenital heart defects.
• Klinefelter syndrome: a chromosomal aneuploidy characterized by the presence of 1 or more extra X chromosomes in a male karyotype, most commonly leading to the karyotype 47,XXY. Klinefelter syndrome is associated with decreased levels of testosterone and is the most common cause of congenital hypogonadism. Individuals with the syndrome tend to present as tall, phenotypic men with small testes, decreased body hair, gynecomastia, and infertility.
• Turner syndrome: a genetic condition affecting women in whom 1 X chromosome is partly or completely missing. The classic result is the karyotype 45,X0 with a female phenotype. The characteristic appearance is that of a female person with short stature, a webbed neck, a broad chest with widely spaced nipples, a low posterior hairline, and peripheral edema of the hands and feet.