MADRID, 14 (EUROPA PRESS)
Eggs deliberately slow down their internal waste disposal systems as they mature, allowing them to maintain low metabolism and minimize damage, remaining dormant for decades until needed, according to a study by the Center for Genomic Regulation (CRG) in Barcelona.
Women are born with between one and two million immature eggs, a reserve that dwindles to a few hundred at menopause. Each egg must withstand wear and tear for up to five decades before it can sustain a pregnancy. Protein recycling is essential for maintenance, and lysosomes and proteasomes are the cell's primary waste disposal units. However, each time these cellular components degrade proteins, they consume energy and can also generate reactive oxygen species (ROS) that can damage DNA and membranes.
In this regard, the research team hypothesized that by slowing recycling, the egg keeps ROS production to a minimum, while performing the maintenance tasks necessary for survival.
The researchers analyzed more than 100 eggs from 21 healthy donors between the ages of 19 and 34. Seventy of these were eggs ready for fertilization, and 30 were still immature. Using fluorescent probes, they tracked lysosomal, proteasomal, and mitochondrial activity in living cells. All three values were approximately 50% lower than those of the eggs' surrounding support cells and decreased further as the cells matured.
Live images showed how the eggs expelled lysosomes into the surrounding fluid during the final hours before ovulation. Simultaneously, mitochondria and proteasomes migrated to the outer edge of the cell. "It's a kind of spring cleaning that we didn't know human eggs could do," says the study's first author, Dr. Gabriele Zaffagnini.
Thus, this research constitutes the largest-scale study of healthy human eggs obtained directly from women, the authors state. To date, most laboratory research has relied on artificially matured eggs in culture dishes; however, these in vitro-matured eggs often exhibit abnormal behavior and are associated with worse IVF outcomes.
Furthermore, this study could lead to new strategies to improve the success rates of the millions of IVF cycles attempted each year worldwide. "Patients with fertility problems are routinely advised to take random supplements to improve egg metabolism," notes Dr. Elvan Böke, one of the study's authors and group leader at the CRG. However, "When looking at freshly donated eggs, we found evidence to suggest that the opposite approach—maintaining the egg's naturally calm metabolism—might be a better idea to preserve quality," he adds.
The team now plans to examine eggs from older donors and from failed IVF cycles to see if limiting the activity of cellular waste-removal units fails with age or disease.
