Because fertility decreases with age

The scientific world continues to repeat to women that fertility decreases drastically over the years because the egg cells are no longer of good quality.

What is the biological reason for this poor quality?

Why do egg cells become “defective”?

Recent research suggests a possible explanation for female age-related infertility.

Using state-of-the-art microscopy techniques, researchers at the University of Montreal Hospital Research Center (CRCHUM) have observed for the first time a specific defect in the eggs of elderly female mice. It has been seen that during that complicated but extraordinary mechanism that leads to cell division, something goes wrong, causing errors in the division of chromosomes.

The researchers saw that the microtubules that orchestrate chromosome segregation during cell division behaved abnormally in aged egg cells.

Instead of creating a lattice by lining up symmetrically, microtubules go in all directions. The altered movement of microtubules therefore seems to contribute to determine errors of chromosomal segregation, thus creating “defective” egg cells.

Women – and other female mammals – are born with a fixed number of oocytes that remain dormant until puberty when, cycle after cycle, they are released, one at a time, during ovulation.

All of this works well until around 35-37 years of age, then something changes and fertility starts to decline.

“Defective” egg cells explain why fertility decreases with age

One of the main causes of female infertility is the presence of “defective” egg cells due to an abnormal number of chromosomes. These aneuploid eggs (that is, having an abnormal number of chromosomes) become more and more numerous as the woman gets older. This is a major reason why women approaching and exceeding 40 have difficulty getting pregnant and carrying it to term. These defective egg cells also increase the risk of early miscarriages as well as the frequency of embryos with chromosomal abnormalities, such as Down’s Syndrome.

Another theory explained the numerical abnormalities of chromosomes with a defect in the “glue” that holds chromosomes together in older cells.

This new theory does not contradict the previous one but demonstrates the existence of another problem: defects in microtubules, which cause defective spindles and which in turn cause errors in the segregation of chromosomes when they are separated and attracted towards the poles of the cell (see figure below where the microtubules are schematized with those brownish filaments and the chromosomes are drawn in purple)

In mice, approximately 50% of eggs from elderly females have microtubule mismatches.

The researchers conducted a series of micromanipulations on the eggs of 6- to 12-week-old mice (juvenile) and 60-week-old (old) mice.

Nuclei from young eggs were swapped for those from old eggs and it was found that segregation problems were also present in old cells containing a young nucleus.

This demonstrates that maternal age influences microtubule alignment independently of the age of the chromosomes contained in the nuclei of each egg.

Researchers hypothesize that the same problem is present in women, where cellular mechanisms work worse over the years regardless of the age of the chromosomes.

This discovery could one day lead to new fertility treatments to help women get pregnant and carry it to term. However, more years of research will be needed to understand how to correct segregation errors.