Human egg cells wait in the ovaries from before birth until they are finally called upon, sometimes 40 years later, to kick start new life.
New research shows that one reason the egg cells last so long is that they run their internal “housekeeping” on a near standby setting, spending as little energy as possible while still keeping themselves tidy.
The work comes from Dr. Elvan Böke and colleagues at the Centre for Genomic Regulation in Barcelona (CRG), who examined more than 100 freshly donated oocytes.
The findings build on earlier reports that oocytes even delete an entire piece of their mitochondrial engine, complex I, to avoid making damaging reactive oxygen species (ROS).
Human eggs stay intact for decades
Women are born with one to two million immature oocytes, yet only a few hundred will ever mature and ovulate.
Keeping those cells intact for decades is a tall order because everyday metabolism creates molecular debris that can harm DNA, membranes, and proteins.
The cell’s main waste bins, the lysosome, and its protein shredding partner, the proteasome, normally burn through fuel as they dismantle old parts.
Every round of degradation consumes energy and risks generating ROS, which can nick chromosomes and shorten the egg’s lifespan.
Earlier work tracked ROS levels during mouse and human oogenesis and saw that eggs hold mitochondrial activity to a minimum, trading speed for safety. The new study takes that idea further by measuring actual lysosomal and proteasomal throughput in live human eggs.
Eggs use less energy to avoid damage
Böke’s team stained live oocytes with fluorescent probes and compared the signal to neighboring cumulus cells that nourish the egg.
Signals from active lysosomes, proteasomes, and mitochondria were roughly half as bright inside the oocyte, confirming an across the board power down.
“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,” said Dr. Böke.
The group also watched mature eggs push lysosomes to the cell edge and eject them into the fluid around the egg, dumping worn parts before ovulation.
“It’s a type of spring cleaning we didn’t know human eggs were capable of,” said Dr. Gabriele Zaffagnini, first author on the study. Few lysosomes remain afterward, and those cluster near the egg’s center, away from mitochondria that migrate toward the rim.
Human eggs ejecting waste
Live cell imaging caught mitochondria and proteasomes forming a loose ring under the membrane in the hours before ovulation. At the same time, the egg jettisons lysosomes, shrinking its waste handling capacity even further.
The researchers did not measure ROS directly but argue that trimming both degradation and respiration likely keeps ROS formation close to zero. That idea fits with biochemical assays showing human oocytes lack detectable complex I activity, a key ROS producer.
Mouse eggs, by contrast, ramp up lysosomal work late in maturation and rely on different compartments called ELVAs to sequester protein aggregates.
The species difference may reflect the weeks long growth of mouse oocytes versus the months long growth in humans, which gives human eggs more time to adopt a slow burn strategy.
What the findings mean for IVF
Around 2.6 million in vitro fertilization (IVF) cycles are attempted worldwide each year, leading to more than half a million births. Yet failure to achieve pregnancy after embryo transfer remains common, and poor egg quality is a major factor.
Most laboratory studies have relied on eggs matured artificially in a dish, a process linked to uneven metabolism and lower success rates.
The new data, built on freshly donated eggs, suggest that the best human oocytes succeed precisely because they stay metabolically quiet until fertilization.
Clinics often recommend antioxidant cocktails or metabolic boosters in hopes of “revving up” tired eggs. Evidence that such supplements actually improve live birth rates is mixed, and some reviews note only modest changes in oocyte numbers or embryo quality.
Keeping eggs quiet may work better
Böke and colleagues propose doing the opposite, preserving the egg’s low power state rather than pushing it. If future trials confirm this idea, IVF protocols might shift toward gentler culture media and timed exposure to avoid waking cellular powerhouses too soon.
A drug that blocks unnecessary proteasome activity or an additive that buffers ROS without raising respiration could, in theory, keep eggs closer to their natural resting mode.
Such interventions would need careful testing because too little housekeeping can be as harmful as too much.
Next steps: Testing older eggs
The team plans to analyze eggs from women over 35 and from failed IVF cycles to see whether the low power program slips with age or disease. If metabolic quietude erodes over time, restoring it could become a targeted therapy for age related infertility.
Basic questions also remain about how human eggs sense when to dump lysosomes or rearrange mitochondria. Answers may reveal new checkpoints that embryos use to gauge human egg quality before development begins.
The study is published in The EMBO Journal.
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