A team at UC San Francisco was mapping ovarian aging and made a huge discovery: it’s impacted by the nervous system.
Thanks to ovary donors, the study was able to compare tissue from women in their twenties and thirties against tissue from women in their mid-to-late fifties. Along the way, they had a larger set of mice spanning their full reproductive lifespan.
Researchers compared ovarian tissue from younger and older donors and found that nerve density increased sharply with age. Women in their late thirties and up had noticeably more nerve fibers than donors in their twenties.
The finding pointed to a potentially major conclusion: the ovary’s nervous system may actively help control which eggs get used over a woman’s reproductive life, not hormones alone.
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Why This Caught Researchers’ Attention
The increase in nerve density was also notably different from what the team saw in mice.
When they measured the same thing in mouse ovaries across a comparable age range, sympathetic nerve density stayed flat.
This contrast alone is helpful for us to better form and understand women’s research using mice. Scientists rely heavily on mice to study human fertility and aging, so when a process like nerve growth behaves differently between species, it’s a sign that mouse data doesn’t always translate cleanly to women.
Nerve density is also one of several places in the study where mouse and human ovarian biology didn’t match, and it pushed the researchers to look more closely at what these nerves were actually doing inside the ovary in the first place.
A Map of the Ovaries
This observation of ovarian aging was part of a larger project: a detailed, side-by-side analysis of mouse and human ovaries. Using 3D tissue imaging and single-cell gene sequencing, the team examined nearly every cell type in the ovary across multiple ages in both species.
It resulted in a map that can be used to understand how the organ is arranged and how it may change over time.
What Does the Map Reveal?
During the research process, they found large networks of nerve fibers running through ovarian tissue in both mice and humans, along with glial cells, which are the support cells that maintain neurons and keep them functioning.
When the researchers checked what kind of nerves these cells were supporting, they found that the large majority of nerve fibers in adult ovaries were sympathetic nerves. Specifically, the same branch of the nervous system that is responsible for the body’s general stress and arousal responses elsewhere.
They also found that these nerves and cells appear early in development, in a similar way between mice and humans. Keeping those nerve fibers alive is a job handled by neighboring cells called pericytes, which pump out a protein called nerve growth factor to feed them.
Testing Whether the Nerves Make a Difference
Finding nerves inside the ovary doesn’t, on its own, prove they matter for fertility. To test that, the researchers used a genetic technique in mice to selectively eliminate the sympathetic nerves supplying the ovary, while leaving the rest of the organ intact.
They did this by removing the receptor that those nerve fibers need to receive the nerve growth factor’s survival signal. Without it, the nerves couldn’t be sustained and largely disappeared from the ovarian tissue.
Mice Eggs Got Left Behind
The effect on the ovary’s egg supply was clear and consistent. Mice without those sympathetic nerves in the ovary ended up with more eggs sitting in their original, dormant state. Significantly fewer eggs had progressed through later stages of growth, particularly the stage just before ovulation.
In other words, removing the nerves didn’t damage or destroy the eggs, but it appeared to stall their progress. Eggs that would normally be pushed toward maturity stayed in reserve, unused.
What Does This Tell Us?
Every woman is born with a fixed, non-renewable supply of immature eggs. The rate at which that supply gets used over a lifetime has long been understood as a result of hormonal signals.
This experiment demonstrates, at least in mice, that the nervous system may also play a direct role in setting the pace at which those eggs get drawn. That makes the documented increase in nerve density in aging human ovaries a candidate for explaining how eggs are recruited and used as women get older.
However, this hasn’t been directly tested in human ovarian tissue.
Decreasing Estrogen
The researchers offered one possible explanation for why ovarian nerve density might increase with age in humans.
Estrogen, which is known in other reproductive tissues to suppress nerve growth, declines as women get closer to menopause.
The researchers think this drop may loosen the brakes on nerve growth, letting nerve fibers expand.
Note: this is the authors’ proposed explanation, not something they proved. The study didn’t actually test what causes the nerve increase in aging human ovaries, but interpreted based on other knowledge.
A Possible Connection to PCOS (Now PMOS)
The study also connects its results to existing knowledge about PCOS, now renamed polyendocrine metabolic ovarian syndrome, one of the most common causes of infertility.
Earlier research has shown that PCOS is linked to unusually high sympathetic nerve activity, along with too many follicles stuck at the antral stage, which is the same stage that dropped sharply when researchers removed sympathetic nerves from mice in this study.
It’s important to note that this study did not test PMOS directly. The researchers are referencing existing research and suggesting a potential direction for future experiments.
What Could This Mean for Women?
The main findings came from experiments in mice: the ovary has an extensive nerve network, which depends on nerve growth factor, and it plays a role in the maturation of eggs. The age-related increase in nerve density was observed directly in human tissue, but researchers haven’t yet tested what that increase actually does in humans, the way they did in mice.
What the study does establish is that the ovary isn’t just a passive structure reacting to hormones from elsewhere in the body. It has its own nervous system wiring, which appears to actively help determine which eggs get recruited and matured, and that wiring changes as women age.
Reproductive aging has long needed a more complete picture, and this research could be the start.
This is an early-stage scientific finding, not medical guidance, and it doesn’t point to any specific action women should take. Anyone with questions about fertility, ovarian health, or conditions like PCOS should talk to a physician or fertility specialist.
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