Older eggs less fertile due to poor cell division

Researchers in Canada have found that age-related infertility may be due to older eggs dividing poorly, leading to errors in chromosome number.

Eggs with an abnormal number of chromosomes (or aneuploid) are a major cause of female infertility and become more prevalent as women age. By comparing egg cells from young and older mice, researchers have found that this may be due to problems with the cell division machinery.

'We found that the microtubules that orchestrate chromosome segregation during cell division behave abnormally in older eggs,' said Professor Greg FitzHarris of the University of Montreal.

Microtubules are tiny cylindrical structures that form an organised pattern to direct chromosomes across cells during division called a spindle. Researchers observed the microtubules in older mouse eggs were sending chromosomes off in all directions, rather than in two controlled, symmetrical groups.

In humans, aneuploid eggs significantly increase after the age of 35. 'This is a key reason that older women have trouble getting pregnant and having full-term pregnancies. It is also known that these defective eggs increase the risk of miscarriage and can cause Down's syndrome in full-term babies,' explained Professor FitzHarris.

Previous studies have shown that in ageing eggs, the 'glue' that keeps chromosomes together doesn't work as it should. The reduced cohesion causes chromosomes to fall apart prematurely during cell division, causing aneuploidy. This is called the 'cohesion-loss' hypothesis. On this hypothesis, Professor FitzHarris noted: 'Our work doesn't contradict that idea, but shows the existence of another problem.'

'When loss of cohesion was suggested as a cause of female infertility, people thought, that’s it, we found the one cause,' Professor FitzHarris told New Scientist. 'But there are certain types of aneuploidy that are well explained by cohesion loss. And there are other types that are harder to explain.'

'In mice, approximately 50 percent of the eggs of older females have a spindle with chaotic microtubule dynamics,' Professor FitzHarris said.

Researchers 'micro-manipulated' the eggs of young and old mice, and used microscopy to visualise the eggs dividing. 'We swapped the nuclei of the young eggs with those of the old eggs and we observed problems in the old eggs containing a young nucleus,' explained Dr Shoma Nakagawa, a postdoctoral research fellow at the University of Montreal. This shows that it is the age of the cell itself, rather than the age of the chromosomes inside the nucleus, that is causing the problem. The authors noted that the microtubule defects were also a problem for humans, with chromosomal defects due to spindle malfunctioning occur in women.

Professor FitzHarris concluded: 'We are currently exploring possible treatments for eggs that might one day make it possible to reverse this problem and rejuvenate the eggs.'

The findings were published in Current Biology.