New research shows that by turning down the internal circulatory system, human eggs can stay viable for decades. Scientists studied more than 100 freshly donated eggs and found that slowing down protein breakdown helps reduce harmful byproducts that can damage DNA. Eggs also undergo a final "spring cleaning" before ovulation, removing waste products and rearranging key components to maintain quality.

Human eggs are among the longest-lived cells in the body, often remaining dormant for decades before being called upon. A new study published in the European Journal of Molecular Biology shows that as these cells mature, they actively reduce the activity of their internal waste disposal mechanisms. This slowing appears to be an evolutionary adaptation designed to keep metabolic levels low for long periods of time and minimize cellular damage.

"By looking at more than a hundred freshly donated eggs, the largest dataset of its kind, we discovered a surprisingly minimalist strategy that helps cells maintain their pristine state for many years," said Dr. Elvan Böke, corresponding author of the study and group leader at the Center for Genomic Regulation (CRG) in Barcelona.

Women are born with one to two million immature eggs, and by menopause, the number gradually dwindles to a few hundred. Each egg must remain in good condition for up to 50 years before it has a chance to participate in reproduction. This study reveals how these cells are able to maintain their integrity for so long.

Within every cell, protein recycling is a critical "household" task. Lysosomes and proteasomes do the job, breaking down old or damaged proteins. However, this process consumes energy and produces reactive oxygen species (ROS), harmful molecules capable of damaging DNA and cell membranes. The researchers did not directly measure ROS in this study, but they propose that by slowing down the rate at which proteins circulate, eggs can limit ROS production while still allowing adequate basic life-sustaining activities.

This finding is consistent with earlier research published by the team in 2022, which found that human oocytes deliberately bypass a key metabolic reaction to further reduce the production of reactive oxygen species (ROS). Together, the two studies show that eggs employ a variety of strategies to reduce metabolic activity and protect themselves from damage for as long as possible.

Immature human oocytes were fixed and immunolabeled with intracellular organelle markers. Mitochondria are shown in orange, endoplasmic reticulum in lavender, and the actin cytoskeleton in green. DNA is shown in light blue. Image credit: Gabriele Zaffagnini/Center for Gene Regulation

The discovery was made after Barcelona fertility clinic Dexeus Mujer collected more than 100 eggs from 21 healthy donors aged 19 to 34, of which 70 were ready for fertilization and 30 were immature oocytes. They used fluorescent probes to track the activity of lysosomes, proteasomes and mitochondria in living cells. The readings for all three activities were about 50% lower than in the supporting cells surrounding the egg itself, and the readings dropped further as the cells matured.

Live imaging shows that in the final hours before ovulation, the egg ejects lysosomes into the surrounding fluid. At the same time, mitochondria and proteasomes migrate to the outer edge of the cell. "This is a kind of 'spring cleaning' that we didn't know human eggs could do," said lead author Dr. Gabriele Zaffanini.

The study is the largest to date to harvest healthy human eggs directly from women. To date, most laboratory studies have relied on artificially matured eggs in petri dishes, however such in vitro matured oocytes often behave abnormally and can lead to poor IVF outcomes.

The research may lead to new strategies to improve the success rate of the millions of in vitro fertilization (IVF) procedures performed around the world each year. "Infertile patients are often advised to take supplements to improve egg metabolism, but there is currently no evidence that these supplements have any benefit on pregnancy outcomes," says Dr. Böke.

She added: "By looking at freshly donated eggs, we found evidence that the opposite approach, maintaining the egg's natural calm metabolism, may be a better way to preserve egg quality."

The team now plans to examine eggs from older donors and failed IVF cycles to see whether limits on cellular waste-disposal unit activity are broken down by age or disease.

Compiled from /scitechdaily