Research into ageing eggs could pave way for fertility-extending treatments

Scientists have developed a new experimental system to study how age-related changes in egg cells make them more prone to chromosomal errors, and whether this decline could potentially be reversed. 

Published in Nature Aging, the research uses mouse egg cells to replicate aging-related changes without waiting for the animals to grow old or collecting aged human eggs, allowing researchers to isolate specific factors contributing to egg deterioration, as explained by Live Science. 

“They have created a tool that's going to allow them to unpick this really beautifully,” said Bettina Mihalas, a postdoctoral fellow at the University of New South Wales not involved in the study. “Being able to tease these mechanisms apart gives you a better scope of what's going on, and allows you to more [precisely] intervene,” she added. 

The study is still in its early stages, but the authors hope it could one day help extend the reproductive windows of women who plan to have children later in life. “Female reproductive aging is a major source of inequity,” said senior author Binyam Mogessie, assistant professor at Yale University School of Medicine. “Women have to make choices men don't have to make.” He noted that in the US, births under age 30 are declining while births over 30 are rising, increasing the risk of chromosomal abnormalities. 

“Even if we can extend this reproductive window by three years, it would be so consequential to the lives of so many people,” Mogessie added.

Ticking biological clock

Women are born with all the egg cells they will ever have, which remain in the ovaries until released through the menstrual cycle. Around age 30, the risk of aneuploidy—eggs carrying the wrong number of chromosomes—begins to rise sharply, growing almost exponentially after 35, and jumping further at 40 and 45. Such abnormalities can cause infertility, pregnancy loss, and genetic disorders in children. 

“The leading theory is that the forces that hold these chromosomes together, before they are separated at fertilization, those forces are failing progressively with age,” Mogessie said. However, this does not fully explain why chromosomal errors spike around age 30. 

To investigate, researchers created a system that triggers “aging-like” changes in eggs, using high-resolution time-lapse microscopy and the gene-editing tool CRISPR to tweak REC8, a protein that acts as a molecular glue for chromosomes. By adding a switch that triggers REC8 degradation, they could simulate aging and control the degree of protein loss in eggs.

The experiment showed that varying levels of REC8 degradation led to errors in chromosome separation and aneuploidy, reflecting what occurs in naturally aged eggs, and revealed a threshold at which errors sharply increased. 

In the future, the model could help screen potential treatments to prevent chromosomal errors, effectively “turning back the clock” on eggs. “It really does set the scene for preventive measures aimed at improving the quality of eggs, at least in an IVF clinic setting,” Mogessie said. “I think that would have a huge impact.”

By Nazrin Sadigova