Human Eggs: The Need, The Risks, The Politics
By Ann A. Kiessling, PhD, The Bedford Research Foundation
October, 2007 The Burrill Stem Cell Report
The tasks of eggs include remodeling gene expression to a state of pluripotency and supporting the first few cleavage divisions with stockpiled biomolecules. The enormous size of mammalian eggs, including human, may play a key role in these tasks. The fully grown human egg, with a diameter of 110 to 120 microns and a volume of approximately 900,000 cubic microns, is nearly 250 times larger than a white blood cell, and nearly 4,000 times larger than a sperm head.
The nucleus of the egg, termed the germinal vesicle, is also huge. With a diameter on the order of 50 microns, the volume of the germinal vesicle is approximately 65,000 cubic microns, more than ten times the volume of a white blood cell. This huge nucleus provides ample open scaffolding for chromatin, a characteristic that may play an important role in gene expression.
The Need for Human Eggs
The egg also has an unusual and unique cell cycle. Oocytes are arrested within the ovary in late G2 of the cell cycle for at least one, and in most cases, several decades. As such, they represent not only the largest, but one of the most quiescent, long-lasting human cells. This is a highly unusual cell cycle arrest point, and the strategy behind this arrest is not known with certainty. In this state, they have twice the normal amount of DNA (tetraploid) and are said to be in the prophase of meiosis. This is the stage at which they stockpile biomolecules for future use and in which chromosome crossover can occur, a process that leads to new combinations of genetic information on each chromosome, giving rise to the genetic uniqueness of each egg.
When the egg is mature, protein and nucleic acid synthesis cease. The huge germinal vesicle migrates to the edge of the oocyte and forms the first metaphase plate adjacent to the plasma membrane, rather than in the center of the cell as in somatic cells. Almost as soon as the metaphase plate is formed, a unique, unequal cell division occurs, which results in the production of the polar body, approximately the size of a somatic cell, which contains a complete set of chromosomes. This is meiosis I. Following the unequal cell division, in contrast to all other cell cycles, the nuclear membrane does not reform around the remaining chromosomes. They immediately undergo a rearrangement, which results in a second metaphase plate. Then the second meiotic arrest occurs [ See Figure 1 ]. The huge cell arrested at metaphase II is very fragile. If not activated within one to two days, the egg will perish.
Several lines of investigation have shown that factors outside the nucleus, in the cell cytoplasm, control the egg’s cell cycle. The transfer of cytoplasm from metaphase II eggs into germinal vesicle-stage eggs initiates meiosis. Molecular characterization of the egg meiosis promoting factor (MPF) revealed it is composed of two cell cycle proteins, Cdc2 and cyclin B [ See Figure 2 ], known cell cycle regulators in somatic cells.
The transfer of cytoplasm from metaphase II eggs into cleaving embryos arrests embryo cleavage at the M phase of the cell cycle. This indicates that metaphase II arrest is also controlled by cytoplasmic factors, termed cytostatic factor (CSF). A serine/threonine kinase, cMos, is an important component of CSF. As shown in Figure 2, cyclin B is synthesized during S phase and complexes with Cdc2. The activation of the complex by Cdc25 leads to kinase activity with a broad spectrum of targets, including other enzymes and structural proteins. Importantly, one of MPF’s targets for phosphorylation early in the M phase is the degradation machinery for cyclin B, which normally occurs after the metaphase plate is fully formed, allowing reformation of the nucleus after cell division in somatic cells. [continued]
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