Researchers have developed a 3D map of an ovary for the first time, enabling a deeper understanding of how and when oocytes — immature eggs — are activated. Published in the journal Nature Aging, the team believes their findings have important implications for human reproductive health, as well as opening the door to future studies.
Researchers used high-resolution microscopy and artificial intelligence to count individual oocytes within mouse ovaries across their lifespan. This enabled them to develop a three-dimensional map of the changes in the ovary over time. In total, they analyzed over 85,000 oocytes from 100 mouse ovaries.
“We measured the number and position of every single oocyte in the ovary across the reproductive lifespan of the mouse,” Elvan Böke, group leader at the Centre for Genomic Regulation (CRG) in Barcelona and senior author of the study, told Discover.
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How Oocyte Activation May Be Regulated
What they found is that the same percentage of oocytes — around 14 percent in mice — are activated in the ovaries at any given time. That suggests a mechanism of regulating their activation, be it a hormone or something else that remains unknown. They believe this fixed fraction of oocyte activation may run across other mammals, not only mice.
Explore All Options“The fact that the fraction of newly activated oocytes doesn't change with age suggests that oocyte activation is regulated,” Böke said. For the team, that reframes the ovaries as an “actively monitored system” that counts its own supply, rather than a passive reservoir of eggs as previously suggested, according to the Barcelona Institute of Science and Technology.
“It could be that every oocyte themself contributes to a signal that allows the ovary, or perhaps the organism more broadly, to sense the size of the remaining reserve,” she said. “We don’t yet know what that signal might be or how this regulation works.”
Applying These Findings to Humans
There are challenges in applying these findings directly to human health, according to the researchers. Mice, like humans, are born with a set number of oocytes. Yet in mice, that stands at 5000 whereas in humans the number is around one million at birth, which then declines to around 400,000 by the time of puberty. Mice also ovulate every four to five days, whereas in humans that is around every 28 days.
Böke believes the team’s findings highlight the many unknowns about women’s reproductive health that still require further study, as these could directly impact fertility. The fixed fraction of activated oocytes might also apply to human health, for instance, but that remains unclear.
“What requires further study for human health is really to understand what regulates oocyte activation — why some oocytes activate to grow while the majority remain dormant,” she said. “We still know remarkably little about how the ovary controls this process.”
After menopause, when a woman’s reproductive cycle ceases, around 1,000 oocytes are thought to remain.
“It's not that we don't have enough oocytes,” Böke told Discover. “We don't know, for example, whether those that are left are all bad quality, or why they didn't activate.”
With further study, understanding the underlying mechanism could in time be used to delay menopause and prolong the fertility window.
“If we understand why oocytes are being lost without ever being ovulated, we may eventually be able to ask whether these processes can be modulated,” Böke said.
Opening the Door to Further Research
Another surprising finding with health implications is that the study found large differences in oocyte numbers, despite little to no difference between individuals.
“From the human perspective, they are like identical twins, growing up under the same environmental conditions,” said Böke. Yet, there was a three-to-four-fold difference in oocyte numbers between individual mice.
This was present before puberty, which suggests the variation develops early on in their life.
“This was really surprising because it means that there's an important stochastic component in determining the initial size of the ovarian reserve,” Böke added.
If the same applies to humans, oocyte numbers likely vary widely between individuals, which could affect fertility, she said. The difference in humans could also be far larger than observed in mice.
“In humans, there will of course be genetic and environmental influences, but our results suggest there may also be an inherent stochastic component determining how many oocytes an individual has,” Böke said.
The methodology they developed can be used to detect the number of oocytes in a human ovary. Her team is currently seeking approvals for such a study. But Böke said that will be a mammoth undertaking, and the research will take time, as a similar lifespan study is fraught with challenges.
In her view, it opens the door to further research to understand what is regulating activation of oocytes in humans, potentially enabling targeted treatments to support fertility.
“I wish we had had this kind of quantitative map 20 years ago, because it gives us a foundation on which we can now start asking much more mechanistic questions," said Böke.
This article is not offering medical advice and should be used for informational purposes only.
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Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
- This article references information from a study published in Nature Aging: Three-dimensional mapping of intact ovaries reveals the aging dynamics of the ovarian reserve
- This article references information from the Centre for Genomic Regulation
- This article references information from the Barcelona Institute of Science and Technology: First 3D map of ovary throughout reproductive lifespan reveals it counts its own eggs
