A new study published in Science (Oct. 2025) reveals new insights into how the ovary ages, not just the eggs, but the entire tissue ecosystem
Researchers from UC San Francisco and Chan Zuckerberg Biohub San Francisco used advanced 3D imaging and single-cell analysis to study how the ovary changes with age. They found that human eggs are grouped into small clusters, or “follicle pockets,” and that these clusters become fewer and more spread out over time.
The clusters, called follicle pockets, are small groups of follicles (each containing an immature egg) that are nestled together within the outer layer of the ovary, known as the cortex. These clusters act like neighborhoods, the eggs and their surrounding support cells communicate and share resources within that space.
As women age, these “neighborhoods” start to thin out, there are fewer follicles in each cluster, and the overall number of clusters declines. This loss of organization and communication between cells may be one of the reasons fertility decreases with age, even before all the eggs are gone.
They also discovered that the ovary contains its own network of nerve fibers and support cells, which actually increase with age. In mouse studies, when these nerves were removed, it changed how the eggs matured—suggesting that the nervous system plays a key role in ovarian function.
The tissue that surrounds the eggs, called the stroma, also changes with age. It becomes stiffer and more inflamed, which can affect hormone balance and egg development. While mice share many of these same aging patterns, there are still key differences, so findings in animals must be applied carefully to humans.
While the exact reason nerves increase in the ovary with age isn’t fully understood, several mechanisms likely explain it:
- Loss of hormones’ calming effect on nerves: Progesterone, especially, helps regulate the sympathetic nervous system and keeps nerve growth in check. As progesterone declines with age, this restraint is lifted, allowing sympathetic fibers in the ovary to expand and become more active.
- Inflammation and fibrosis stimulate nerve growth: Aging ovarian tissue becomes more inflamed and fibrotic. These changes trigger the release of nerve growth factor (NGF) and other signaling molecules that encourage new nerve formation.
- Increased oxidative stress and mitochondrial decline: As energy production weakens with age, oxidative stress rises. This can activate repair pathways that promote nerve sprouting as the body tries to maintain communication and function.
- Hormonal imbalance amplifies signaling: With less progesterone to oppose estrogen, the ovary becomes more reactive to stress signals, creating a feedback loop of inflammation, nerve activation, and impaired tissue repair.
A few takeaways:
- This study shifts the paradigm of ovarian ageing from “just the egg loses quality” to “the whole ovarian ecosystem changes” (eg, nerves, support cells, structure).
- It suggests that fertility decline and the onset of menopause may be driven as much by changes in the tissue environment (nerve signalling, inflammation, stiffness) as by the depletion of eggs.
- Because ovarian health is tied to broader outcomes (cardiovascular risk, bone health, hormonal balance), preserving the ovarian ecosystem may have implications far beyond just fertility.
- Think of the ovary as part of a metabolic and neurological system, not just a “vault of eggs.” It’s a dynamic organ that responds to signals from the brain, the endocrine system, and the body’s metabolic state. The nerves, blood vessels, and connective tissue within the ovary create a complex communication network that influences how eggs mature and how hormones are produced.
- Supporting nerve and vascular health, reducing inflammation and fibrosis in the surrounding tissue, and maintaining mitochondrial energy production all help preserve ovarian function. When circulation and oxygen delivery are strong, and the tissue environment remains flexible and well-nourished, eggs develop in a more stable and less inflammatory setting.
- Lifestyle choices that nurture this ecosystem—adequate protein and micronutrients, balanced hormones (especially progesterone and thyroid), stress reduction, restorative sleep, and avoidance of endocrine disruptors—help sustain the ovary as a living, responsive organ. These terrain-focused strategies can have just as much impact on long-term fertility and hormonal balance as any egg-targeted intervention.
This study reframes ovarian health as an energy and communication problem, not just a numbers game. To protect and stabilize the ovaries we need to support the entire terrain: improving circulation, reducing inflammation, maintaining mitochondrial energy production, and supporting hormones like progesterone.