Research: Eggs are smart: they save energy while waiting to be fertilized.

For scientists who have studied them in detail, they are "among the most patient cells in the human body." Decades can pass before their moment arrives, and while they wait, persevering eggs slow down their internal systems to a crawl, entering a sort of "anti-wear and tear hibernation" that allows them to remain dormant while awaiting fertilization.

This unprecedented "gift" is described in a study recently published in The Embo Journal, which shows how these cells deliberately slow down certain processes. Most likely, according to the authors, this is an evolutionary design that keeps the metabolism low and prevents damage. "By looking at more than one hundred newly donated eggs—the largest dataset of its kind—we discovered a surprisingly 'minimalist' strategy that helps the cells remain pristine for many years," explains Elvan Böke, corresponding author of the study and Group Leader at the Center for Genomic Regulation in Barcelona. Women are born with 1 to 2 million immature eggs, a reserve that drops to a few hundred during menopause. Each egg must withstand wear and tear for decades before it can sustain a pregnancy. The new study suggests how this process is managed and what was discovered could be applied to improving in vitro fertilization techniques.

Protein recycling is an essential activity for cell housekeeping, and lysosomes and proteasomes are the main waste disposal units. However, each time these cellular components degrade proteins, they consume energy. This in turn can create reactive oxygen species (ROS), molecules that can damage DNA and membranes. The team did not directly measure ROS, but hypothesizes that by curbing recycling, the egg keeps the production of these harmful molecules to a minimum while continuing to perform the housekeeping tasks necessary for survival. This idea aligns with the group's previous work, published in 2022, and together, the two studies suggest that human oocytes self-regulate in different ways to minimize potential damage and survive as long as possible.

The discovery was made possible by collecting over 100 eggs from 21 healthy donors aged 19 to 34 at the Dexeus Mujer fertility clinic in Barcelona, including 70 eggs ready for fertilization and 30 immature oocytes. Using fluorescent probes, experts monitored the activity of lysosomes, proteasomes, and mitochondria in the living cells. All three readings were approximately 50% lower than in the supporting cells surrounding the eggs and decreased further as the cells matured. Live imaging then showed that, during the final hours before ovulation, the eggs "revived" and literally released lysosomes into the surrounding fluid. At the same time, mitochondria and proteasomes migrated toward the outer edge of the cell. "It's a type of 'spring cleaning' that we didn't know they were capable of," says first author Gabriele Zaffagnini. The research is the largest study on healthy human eggs collected directly from women. Most laboratory research to date has relied on eggs artificially matured in vitro, yet these in vitro matured eggs often behave abnormally and are associated with poorer outcomes in in vitro fertilization.

The study could lead to new strategies to improve the success rates of the millions of IVF cycles attempted each year worldwide. "Infertile patients are regularly advised to take random supplements to improve egg metabolism, but evidence of any benefit for pregnancy is patchy," says Böke. "By looking at newly donated eggs, we found evidence suggesting that the opposite approach—maintaining the egg's naturally 'silent' metabolism—might be a better idea to preserve its quality," he adds. The team now plans to examine eggs from older donors and from failed IVF cycles to see whether the activity of the cellular waste disposal units is slowed by age or disease.