All women of a certain age are keenly aware that their fertility begins to decline significantly around age 35, but have you ever stopped to wonder why? Or if there was anything that could be done about it?

Scientists at the University of Montreal Hospital Research Center (CRCHUM) say they have observed a specific defect in the eggs of older mice that they believe may have a parallel in the eggs of older women. The defect caused the cell division to fall out of step and generate errors in the sharing of chromosomes.

"We found that the microtubules that orchestrate chromosome segregation during cell division behave abnormally in older eggs. Instead of assembling a spindle in a controlled symmetrical fashion, the microtubules go in all directions. The altered movement of the microtubules apparently contributes to errors in chromosome segregation, and so represents a new explanation for age-related infertility," stated CRCHUM researcher and University of Montreal professor Greg FitzHarris.

Microtubules are tiny cylindrical structures that organize themselves to form a spindle. This complex biological machine gathers the chromosomes together and sorts them at the time of cell division, then sends them to the opposite poles of the daughter cells in a process called chromosome segregation.

Women – and their mammal-kingdom counterparts – are all born with a set number of eggs. These lay low in the ovaries, yielding one egg during each menstrual cycle..

"One of the main causes of female infertility is a defect in the eggs that causes them to have an abnormal number of chromosomes. These so-called aneuploid eggs become increasingly prevalent as a woman ages. 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 FitzHarris.

The previous theory regarding why fertility declines with age had to do with the quality of the “glue” that keeps chromosomes together. Called the “cohesion-loss” hypothesis, it upheld that as the chromosomal “glue” aged, it didn't hold up as well. And that may still be all or part of the problem.

"Our work doesn't contradict that idea, but shows the existence of another problem: defects in the microtubules, which cause defective spindles and in doing so seem to contribute to a specific type of chromosome segregation error" said FitzHarris.

The researchers swapped the nuclei of the young eggs with those of the old eggs and we noticed problems in the old eggs containing a young nucleus. They believe that this shows that maternal age influences the alignment of microtubules independently of the age of the chromosomes contained in the nuclei of each egg.

Next steps? The scientists recognize that it will take many more years of research before they will have any actionable mechanism which could lead to new fertility treatments to help women become pregnant and carry a pregnancy to term, but the goal is clearly in their field of vision.

"We are currently exploring possible treatments for eggs that might one day make it possible to reverse this problem and rejuvenate the eggs," said FitzHarris.

The research was published in CurrentBiology.