Human Eggs Exhibit Protective 'Power-Down' Mechanism, Research Reveals

A recent study published in *The EMBO Journal* uncovers a significant protective mechanism in human eggs, which enter a state of reduced metabolic activity to maintain cellular integrity over decades. This research, led by Dr. Elvan Böke, Group Leader at the Centre for Genomic Regulation (CRG) in Barcelona, represents the largest dataset of its kind analyzed, comprising over 100 freshly donated eggs from 21 healthy women aged 19 to 34.

Human eggs, or oocytes, begin their development in the ovaries when women are born, with estimates of one to two million immature eggs at birth. This number declines to a mere few hundred by the time of menopause, necessitating the need for these cells to remain viable for potentially up to five decades before they can support a pregnancy. The study reveals that as eggs mature, they intentionally slow down the activity of their internal waste disposal systems, thereby minimizing metabolic activity and reducing the risk of cellular damage.

Dr. Böke states, "By looking at more than a hundred freshly donated eggs, we found a surprisingly minimalist strategy that helps the cells stay pristine for many years." The study highlights that human eggs manage to power down their metabolic processes, particularly the recycling of proteins, which is essential for cellular housekeeping. The lysosomes and proteasomes—the primary waste disposal units of the cell—were found to operate at about 50% lower activity than surrounding support cells, further decreasing as the eggs matured.

The researchers hypothesize that by throttling these recycling mechanisms, the eggs can keep the production of reactive oxygen species (ROS)—molecules that can lead to DNA and membrane damage—to a minimum. Although direct measurements of ROS were not conducted, this conjecture aligns with findings from previous studies indicating that oocytes deliberately skip fundamental metabolic reactions to curb ROS production.

The groundbreaking nature of this study stems from its methodology, which contrasts sharply with prior research that heavily relied on artificially matured eggs. Dr. Gabriele Zaffagnini, the first author of the study, expresses that this research reveals a type of 'spring cleaning' that human eggs can perform as they mature. The study's findings suggest that the eggs literally expel lysosomes into the surrounding fluid as they approach ovulation, while simultaneously relocating mitochondria and proteasomes to the outer edge of the cell.

These findings hold significant implications for assisted reproductive technology (ART), particularly in in vitro fertilization (IVF). According to Dr. Böke, current fertility practices often recommend various supplements to enhance egg metabolism; however, evidence supporting their efficacy for improving pregnancy outcomes is inconsistent. This research advocates for maintaining the egg's naturally reduced metabolic state as a more effective strategy for preserving egg quality.

The team plans to extend their research to examine eggs from older donors and those from unsuccessful IVF cycles to determine if the power-down mechanism diminishes with age or disease. Overall, this study not only advances the understanding of egg biology but also opens new avenues for improving IVF success rates worldwide, potentially benefiting millions of couples facing fertility challenges.

This research exemplifies a critical step forward in reproductive biology, illuminating the extraordinary adaptations of human eggs to survive extensive periods of dormancy while retaining their vital functions for future reproductive success.