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Explaining mammal egg errors

27 October 2003
By BioNews
Appeared in BioNews 231

As many as a fifth of a woman's eggs are genetically scrambled - but it's not because they can't check their chromosomes, say a team of UK and French scientists. A new study published in the journal Reproduction shows that egg-producing cells in mammals have a mechanism for checking their chromosomes when they divide, just like those present in other animal species. So, the explanation for the high rate of chromosome errors in the eggs of humans and other mammals must lie elsewhere, say the researchers, based at laboratories in Paris and the University of Manchester.

Nearly all human body cells have a set of 46 chromosomes (22 pairs plus two sex chromosomes), whereas egg and sperm cells have 23 (one from each pair plus either an X or Y chromosome). To make egg and sperm, a cell with 46 chromosomes must first divide into two, in a way that ensures that the resulting 'daughter' cells both have half the number of chromosomes of the original cell. A second round of cell division sees each chromosome split along its length into two identical strands - one for each of the daughter cells. This whole process is known as meiosis. To ensure that all four daughter cells get a complete, accurate set of genetic instructions, the chromosomes must 'line up' along the centre of the cell before it divides. Like a teacher picking two sports teams, each half of the cell then gets one chromosome from each pair (or one strand from each chromosome when the cells divide for the second time).

But it seems that, at least in humans, female meiosis is extremely inefficient: around 20 per cent of newly fertilised eggs have the wrong number of chromosomes in them. Most of these eggs cannot begin to grow, but sometimes, as in Down syndrome, the embryo can still develop. Down syndrome occurs when three copies of chromosome 21 are present, usually after an egg cell with two copies of chromosome 21, rather than just one, is fertilised by a normal sperm. Previously, scientists thought that this type of error could be down to the lack of a checking mechanism called the 'spindle checkpoint': a collection of proteins that usually marshals the chromosomes when they line up in the middle of the cell before it divides. But the new study shows that, in mice at least, a working spindle checkpoint does seem to be present during egg cell production. So something else must be causing the high egg error rate in mammals, say the authors - perhaps the checkpoint is 'silenced' in older egg-producing cells. 'The mechanism of such a process remains to be investigated' they conclude.

Functionality of the spindle checkpoint during the first meiotic division of mammalian oocytes
Reproduction |  1 October 2003
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