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Scientists pinpoint age-related errors in human eggs

Paired copies of chromosomes separating early can cause issues during pregnancy, as well as genetic diseases in children.

By Stephen Feller

SAITAMA, Japan, July 1 (UPI) -- As egg cells mature in older women, researchers have found that pairs of chromosomes separate at the wrong time, leading to early division of chromosomes and incorrect segregation of into mature cells.

Eggs that form with the wrong number of chromosomes often result in miscarriage or genetic diseases such as Down syndrome.

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Cells ordinarily have two copies of each chromosome, one from each parent. Immature egg cells begin the same way, but mature through the process of meiosis to to have just one copy of each chromosome. At the beginning of meiosis, the process of cell replication and division, the chromosomes copy themselves and then join with their copy, forming a group of 4 chromosomes called a bivalent, within which they swap genetic material. The bivalent then splits into single pairs, one copy of each chromosome, and the cell divides. One part continues as the cell and the other degrades.

The second stage of meiosis works the same way as the single pairs of chromosomes, called sister chromatids, separate, and the egg cell divides the same way as in the first stage. This leaves one mature egg with a copy of each chromosome.

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"What we found is that in older cells, the bivalents sometimes separate early, and this leads to division of sister chromatids in the first stage of meiosis, rather than in the second stage," said Tomoya Kitajima, of the Laboratory for Chromosome Segregation at the RIKEN Center for Developmental Biology, in a press release.

To find the event in cell division that causes problems with older eggs, researchers watched chromosomes in live mouse egg cells throughout the first stage of meiosis, finding the younger cells' chromosomes were always correctly distributed but that in older cells 10 percent had segregation errors.

The reason for the early separation, researchers found, was the chromosomes had been part of bivalents whose connection between paired copies had become hyperstretched and then snapped.

"We were surprised and pleased that the vast majority of errors are preceded by a single common event -- bivalent separation," says Kitajima. "Now we can focus our efforts on developing an artificial tie to suppress premature separation and on understanding the molecular mechanism underlying the age-related reduction in bivalent cohesion that appears to precede it."

The study is published in Nature Communications.

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