In normal tissues, molecules such as hormones, growth factors and cytokines provide the signal to activate the cell cycle: a controlled pro gramme of biochemical events that culminates in cel division. In all cels of the body, except the gametes (the sperm and egg cels, also known as the germ line), mitosis completes cel division, resulting in two diploid daughter cells. In contrast, the sperm and eggs cells complete cell division with meiosis, resulting in four haploid daughter cells (Fig. 1).
Fig1. Meiosis and gametogenesis: the main chromosomal stages of meiosis in both males and females. A single homologous pair of chromosomes is represented in different colors. The final step is the production of haploid germ cells. Each round of meiosis in the male results in four sperm cells; in the female, however, only one egg cell is produced, as the other divisions are sequestered on the periphery of the mature egg as peripheral polar bodies.
The stages of cell division in the non-germ-line, somatic cells are shown below:
● Cells not committed to mitosis are said to be in G0
● Cells committed to mitosis must go through the preparatory phase of interphase consisting of G1 , S and G2
● G1 (first gap): synthesis of the cellular components necessary to complete cell division
● S (synthesis): DNA replication producing identical copies of each chromosome called the sister chromatids
● G2 (second gap): repair of any errors in the replicated DNA before proceeding to mitosis.
● Mitosis (M) consists of four phases:
● Prophase: the chromosomes condense and become visible, the centrioles move to opposite ends of the cell and the nuclear membrane disappears.
● Metaphase: the centrioles complete their migration to opposite ends of the cell and the chromosomes – consisting of two identical sister chromatids – line up at the equator of the cell.
● Anaphase: spindle fibres attach to the chromosome and pull the sister chromatids apart.
● Telophase: the chromosomes decondense, the nuclear membrane reforms and two daughter cells – each with 46 chromosomes – are formed.
The progression from one phase to the next is tightly controlled by cell-cycle checkpoints. For example, the checkpoint between G2 and mitosis ensures that all damaged DNA is repaired prior to segregation of the chromosomes. Failure of these control processes is a crucial driver in the pathogenesis of cancer, as discussed on page 130.
● Meiosis is a special, gamete-specific, form of cell division (see Fig. 1). Like mitosis, meiosis consists of four phases (prophase, metaphase, anaphase and telophase) but differs from mitosis in the following ways:
● It consists of two separate cell divisions known as meiosis I and meiosis II.
● It reduces the chromosome number from the diploid to the haploid number via a tetraploid stage, i.e. from 46 to 92 (MI S) to 46 (MI M) to 23 (MII M) chromosomes, so that when a sperm cell fertillises the egg, the resulting zygote will return to a diploid, 46, chromosome complement. This reduction to the haploid number occurs at the end of meiosis II.
● The 92 chromosome stage consists of 23 homologous pairs of sister chromatids, which then swap genetic material, a process known as recombination. This occurs at the end of MI prophase and ensures that the chromosome that a parent passes to his or her offspring is a mix of the chromosomes that the parent inherited from his or her own mother and father.
The individual steps in meiotic cell division are similar in males and females. However, the timing of the cell divisions is very different. In females, meiosis begins in fetal life but does not complete until after ovulation. A single meiotic cell division can thus take more than 40 years to complete. As women become older, the separation of chromosomes at meiosis II becomes less efficient. That is why the risk of trisomies due to non-disjunction grows greater with increasing maternal age. In males, meiotic division does not begin until puberty and continues throughout life. In the testes, both meiotic divisions are completed in a matter of days.
