Human eggs are remarkable for their longevity, lying dormant for decades—often up to 50 years—before they may be called upon to support a pregnancy. A new study published in The EMBO Journal sheds light on how these cells maintain their integrity for so long: by deliberately slowing down their internal waste management systems, likely as an evolutionary safeguard to minimize metabolic stress and cellular damage.

“By looking at more than a hundred freshly donated eggs, the largest dataset of its kind, we found a surprisingly minimalist strategy that helps the cells stay pristine for many years,” says Dr. Elvan Böke, corresponding author of the study and Group Leader at the Centre for Genomic Regulation (CRG) in Barcelona.

Minimal Metabolism for Maximum Longevity

Women are born with one to two million immature eggs, but only a few hundred survive into the reproductive years. Each of these eggs must remain viable for decades, facing threats like reactive oxygen species (ROS), which can damage DNA and membranes over time.

Protein recycling, handled by lysosomes and proteasomes, is essential for cell maintenance—but it’s also energy-intensive. This energy use can inadvertently generate ROS. While the researchers didn’t measure ROS directly, they propose that by slowing recycling activity, human eggs reduce ROS production while still performing essential upkeep.

This idea builds on the group’s 2022 findings, which revealed that human oocytes intentionally bypass a key metabolic process to reduce ROS levels. Together, the studies suggest that human eggs adopt a “power down” strategy in multiple ways to avoid internal damage.

Spring Cleaning Before Ovulation

The research was based on an unprecedented dataset of over 100 eggs collected from 21 healthy donors aged 19 to 34 at the Dexeus Mujer fertility clinic in Barcelona. Seventy of these were fertilization-ready, while 30 were still immature. Using fluorescent probes, the team tracked lysosome, proteasome, and mitochondrial activity in live cells.

All three types of cellular activity were about 50% lower in eggs compared to their surrounding support cells—and dropped even further as the eggs matured. Live-imaging captured a fascinating sight: eggs actively ejecting lysosomes into the surrounding fluid just before ovulation. Meanwhile, mitochondria and proteasomes moved toward the cell’s outer edge.

“It’s a type of spring cleaning we didn’t know human eggs were capable of,” says first author Dr. Gabriele Zaffagnini.

The study is notable for being the largest analysis of healthy, naturally matured human eggs. Most previous research has used eggs matured artificially in vitro, which often behave abnormally and result in lower IVF success rates.

Rethinking Egg Health in IVF

These findings may inform new strategies to boost the success of in vitro fertilization (IVF), which is attempted millions of times globally each year. Current approaches often focus on boosting egg metabolism with supplements—despite little scientific support.

“Fertility patients are routinely advised to take random supplements to improve egg metabolism, but evidence for any benefit for pregnant outcomes is patchy,” says Dr. Böke.

“By looking at freshly-donated eggs we’ve found evidence to suggest the opposite approach, maintaining the egg’s naturally quiet metabolism, could be a better idea for preserving quality,” she adds.

Next, the team plans to investigate whether this low-activity state is compromised in eggs from older donors or those involved in unsuccessful IVF cycles, potentially unlocking more answers about age-related infertility.

Original Publication
Authors: Gabriele Zaffagnini, Miquel Solé, Juan Manuel Duran, Nikolaos P Polyzos and Elvan Böke.
Journal: The EMBO Journal
DOI: 10.1038/s44318-025-00493-2
Method of Research: Experimental study
Subject of Research: Human tissue samples
Article Title: The proteostatic landscape of healthy human oocytes
Article Publication Date: 16-Jul-2025