Human egg cells, or oocytes, utilize a sophisticated internal housekeeping mechanism to maintain DNA integrity over decades, with this process intensifying just before ovulation. Research from Barcelona's Centre for Genomic Regulation (CRG) reveals that these cells deliberately slow their waste removal systems, a strategy that helps maintain a low metabolism and minimize damage over extended periods. Women are born with a finite reserve of one to two million immature eggs, a number that significantly decreases by menopause. Each oocyte must remain viable for up to fifty years, highlighting their remarkable resilience.
Cellular maintenance relies on protein recycling, primarily managed by lysosomes and proteasomes. However, this process consumes energy and can generate reactive oxygen species (ROS), which can harm DNA and cellular membranes. The CRG study, analyzing over 100 eggs from 21 healthy donors aged 19 to 34, found that the activity of these waste disposal units is approximately 50% lower in egg cells compared to their surrounding support cells, with this activity further decreasing as the eggs mature. In a process described as "spring cleaning," live imaging demonstrated that human eggs expel lysosomes into the surrounding fluid in the hours preceding ovulation. Simultaneously, mitochondria and proteasomes are repositioned to the cell's periphery. This meticulous internal reorganization is crucial for preserving egg quality. The findings suggest that by reducing the pace of protein recycling, eggs limit ROS production while still performing essential maintenance for survival. This research, representing the largest study of healthy human eggs obtained directly from women, contrasts with much previous laboratory work that relied on artificially matured oocytes, which often exhibit abnormal behavior and are linked to poorer outcomes in in vitro fertilization (IVF). The insights gained could pave the way for new strategies to enhance the success rates of IVF cycles globally. Instead of advising random supplements to boost egg metabolism, this study suggests that maintaining the egg's naturally quiescent metabolic state might be a more effective approach for preserving quality. The team plans to further investigate eggs from older donors and those from failed IVF cycles to understand if the regulation of cellular waste removal falters with age or disease, aiming to deepen the understanding of how these vital cells safeguard their genetic material and potentially improve fertility treatments and address age-related declines in reproductive health.