The events that happen before life begins can go wrong surprisingly often.
An important one is meiosis, where cells divide to produce the egg and sperm. When the egg is developing, meiosis involves two rounds of division where genetic material on chromosomes is shuffled, or recombined, and half the chromosomes are pulled into an egg cell, ready to be fertilised.
When this fails, the egg has the wrong number of chromosomes and an embryo will rarely develop.
Now a team led by Terry Hessold of Washington State University, US, has found that human oocytes – immature human egg cells – contain an unbalanced number of chromosomes around 7% of the time. This suggests that improper meiosis is surprisingly common, regardless of a mother’s age.
“From our experience counselling couples who have experienced a miscarriage or the birth of a child with an extra or missing chromosome, it is clear that there is frequently accompanying guilt,” says Hassold. “Our results indicate that quite the contrary, many of these chromosome errors are simply hardwired into human biology.”
Meiotic failure leads to aneuploidy, where the cells have the wrong number of chromosomes. While aneuploidy has been known about for a long time, the frequency of this occurring was not previously determined, because it is very difficult to track recombination in oocytes.
To understand this, the team examined 7396 oocytes from 160 tissue samples. They scanned the oocytes for the presence of a protein, MLH1, that indicates recombination.
They found that at least 7% of the oocytes had at least one chromosome pair that didn’t recombine but estimate that the real frequency of failure is closer to 10%-15%.
“Probably the most surprising observation was simply the high proportion of eggs that contained exchange less chromosomes,” says Hassold. “We had known from previous preliminary studies and from trisomic pregnancies that the value would be high, but seeing it directly in human eggs was still a little jarring.”
The chromosomes that failed recombination the most were the small chromosomes, chromosome 21 and 22. Three copies of chromosomes 21 is the cause of Down syndrome.
They also found that the likelihood of this happening was only very slightly higher in older mothers. Previously, it was through that age was a big contributor to aneuploidy, but this suggests there isn’t a major difference.
“We have known for a long time that advancing maternal age increases the likelihood of chromosomally abnormal eggs, but this observation demonstrates that many chromosome errors have nothing to do with maternal age,” says Hassold. “They are, instead, errors that are extremely common in our species, for reasons that are unclear.”
In the future, the researchers hope to study other genetic factors that may lead to failed recombination.
Their latest findings are published in the American Journal of Human Genetics.