Weaker mitochondrial activity might explain why older eggs mature less often

In a 2025 study, researchers found that poor mitochondrial activity limits the ability of immature eggs to reach maturity, leading to reduced maturation in eggs from older women.

Mitochondria are the egg’s power source, and their function declines with age. Older eggs often have fewer mitochondria, more damage in mitochondrial DNA (mtDNA), and less efficient energy production, which can contribute to aneuploidy and lower embryo quality.

But it’s not clear if this mitochondrial dysfunction actually affects the egg’s ability to mature in the first place, or if it only matters later during fertilization and early embryo development.

A study by Pietroforte et al. (2025) looked at immature eggs from younger and older women to see how their mitochondrial activity changed as the eggs matured, and whether those metabolic patterns were linked to successful or failed maturation. In other words, are mitochondrial differences just a feature of aging eggs, or are they part of the reason some eggs fail to mature?

To do this, researchers collected immature germinal-vesicle (GV) eggs from women undergoing IVF, then matured them in the lab for 30 hours (ie. they essentially performed rescue IVM). Throughout this process, they monitored mitochondrial activity using two approaches:

Imaging of mitochondrial proteins to estimate activity and number
Live metabolic imaging (FLIM) to track NAD(P)H and FAD⁺ — natural signals tied to energy production

They compared eggs from younger women (≤34) and women of advanced maternal age (>37), and they also ran a small experiment where they temporarily reduced mitochondrial function in young eggs to see how that affected maturation.

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Younger and older eggs show very different mitochondrial activity during maturation

When they monitored NAD(P)H intensity in the eggs, they found that there was a 4% increase in mitochondrial activity while eggs progressed from the immature stage (GV) to the mature stage (M2). This shows that eggs actually increase mitochondrial activity as they mature.

Next, they wanted to see if there were any differences between young and old oocytes:

Older eggs tended to have smaller, rounder mitochondria that fused less often, which implies weaker energy production during maturation.
Younger GV eggs had stronger mitochondrial activity, while older GV eggs had much weaker activity, even though the overall number of mitochondria wasn’t very different.
Younger eggs showed a small, steady rise in mitochondrial activity as they matured, but older eggs either showed no rise at all or wild, erratic swings in their activity levels. Older eggs that failed to mature showed much more erratic metabolic behavior than ones that matured.
This was linked to reduced maturation: 62.3% of older eggs matured vs 86.3% of younger eggs (p< 0.01).

This suggests that older eggs don’t just have weaker mitochondrial activity, but they also struggle to keep it stable, and this instability may be part of why fewer of them reach MII.

Suppressing mitochondrial activity leads to reduced egg maturity

Since they found that mitochondrial activity drops with age, and that this is linked to reduced egg maturity, the researchers wanted to see if mitochondria are what cause this change.

To do this, they used a chemical called FCCP to specifically suppress mitochondrial activity in young eggs, which reduced their maturity from 86.3% to 39.5% (p< 0.001).

This shows that mitochondrial activity isn’t just correlated with egg maturity, it actually causes it.

Conclusions

This study showed that eggs normally increase their mitochondrial activity as they mature, and younger eggs did this consistently. Older eggs started with weaker mitochondrial activity and often showed little or no rise, or more erratic behavior, which was linked to lower maturation rates.

When the researchers suppressed mitochondrial activity in young eggs using a chemical, their ability to mature dropped sharply. This shows that normal mitochondrial activity is required for an egg to complete maturation.

They also noticed something else important: older eggs that failed to mature had much more erratic metabolic behavior than those that succeeded. This suggests that the problem isn’t only low activity, but instability may play an important role. The authors note that this supports the idea that eggs need their metabolism to stay within a narrow, balanced “Goldilocks range” during maturation: not too high, not too low, and not wildly fluctuating.

Limitations: This was lab-based work using GV oocytes that didn’t mature after stimulation, which may not match eggs maturing naturally inside the follicle. They also measured metabolism indirectly and didn’t assess chromosome quality, so we can’t say whether metabolic problems lead to aneuploidy or poor embryo development.

Want to read more about mitochondrial health and IVF?

The egg cell contains a high number of mitochondria, which are tiny cellular organs that produce energy that the egg needs to power fertilization and embryo development. Research has shown that these mitochondria can become dysfunctional with age, leading to reduced energy availability for the egg that could result in poor egg quality. Different treatments that target mitochondria, like antioxidant supplements or mitochondrial donation, may improve egg quality, although good quality research is lacking that shows these treatments are truly effective. Read more.

Mini “MRI” reads embryo metabolism to help pick the best embryo for IVF

In a 2025 study, researchers tested a noninvasive MRI-like tool that reads an embryo’s metabolic health, accurately predicting which would stop developing and potentially helping select the healthiest for transfer. Read more.

Ovarian stimulation may harm egg quality through mitochondrial stress

A pilot study in 2025 explored whether mitochondrial DNA mutations in follicular fluid could reflect egg quality, finding some early signs of a possible link, but there were some significant limitations. Read more.

Reference

Sara Pietroforte, Marion Martins, Montserrat Barragan, Elena Ibañez, Rita Vassena, Mina Popovic, Tim Sanchez, Denny Sakkas, Filippo Zambelli, Mitochondrial metabolism influences meiotic maturation in human oocytes of young and advanced maternal age women, Human Reproduction, 2025;, deaf207, https://doi.org/10.1093/humrep/deaf207

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.