Debate erupts over whether ovaries can remake eggs

oogonial stem – For decades, biology taught that women are born with a fixed egg supply that simply dwindles until menopause. New findings—ranging from mouse experiments to studies of adult human ovarian tissue—challenge that “fixed egg pool” idea and suggest adult ovaries ma

When Jonathan Tilly talks about infertility and menopause, he doesn’t start with the traditional answer. He starts with a question: what if women don’t run out of eggs in the simple way textbooks have long described?

The idea has been around so long it feels like biology’s backbone. For roughly 70 years. scientists have taught that female mammals are born with a finite ovarian egg supply that declines steadily over the lifespan. In humans, that reserve dwindles until menopause, when it is often described as effectively “bankrupt.”.

Now a growing body of research is pushing against that dogma. Over the past two decades. scientists have identified cells in the adult ovaries of mice. cows. pigs. non-human primates. and humans that—under certain conditions—appear capable of generating new immature egg cells. known as oocytes. The big uncertainty isn’t whether new oocyte-like cells can be seen; it’s whether those cells can produce viable eggs. Even so. the findings have ignited a contentious debate in reproductive biology. and a controversial possibility is taking shape: ovarian aging may be far more dynamic than previously assumed—and perhaps even reversible.

“Previous to this work, every response to questions about infertility or menopause was rooted in the concept that women only have a fixed number of eggs to work with,” says Jonathan Tilly, a biologist at Northeastern University. “But what if that wasn’t the case?”

The story of why this idea lost and then regained momentum goes back nearly a century. Scientists first proposed that ovaries might generate new eggs through life as early as the 1920s. The argument largely cooled after influential work in the mid-20th century by British scientist Solly Zuckerman. who counted oocytes in animals at different life stages. In his experiments. he didn’t detect the formation of any new oocytes and concluded that ovaries couldn’t make new cells.

For a while, that conclusion set the terms of the debate.

Then. in 2004. Tilly and his team published a paper in Nature arguing that the “fixed egg pool” idea didn’t add up mathematically. Their reasoning turned on follicular atresia—the natural degeneration and death of oocytes before they can potentially become mature eggs. Tilly says the rate at which oocytes died off appeared inconsistent with the number that remained later in life. That discrepancy, he says, pointed toward the possibility that “there must be some kind of new egg production happening.”.

Tilly proposed that specialized stem cells, called oogonial stem cells (OSCs), must be producing new oocytes. The logic was familiar from other parts of the body: stem cells are rare. unspecialized cells that can become a variety of cell types. and they are incredibly useful for bodily repair and regeneration. The question was whether the ovary had its own version of that engine.

In 2009, researchers from Shanghai Jiao Tong University isolated OSCs from adult mice and studied their oocyte-forming ability. In 2012, Tilly and others showed that cells consistent with OSCs could be found in adult human ovaries.

The evidence shifted again in 2017. Tilly’s team engineered female mice with a genetic tool so that any newly formed oocytes would glow fluorescent green under a microscope. The findings suggested that newly generated oocytes didn’t just add to the mice’s ovarian reserve; they could also be used to produce viable mouse offspring.

But if the system can create new oocytes, what happens as the years pass?

In 2023, Tilly’s team reported that OSCs persist into old age in mice yet appear to lose their ability to generate new oocytes as key developmental genes become inactive. That pattern was also seen in human ovarian tissue, and Tilly believes it may explain why OSCs still exist after menopause.

Not everyone is convinced.

Some scientists treat the idea of OSCs with fierce skepticism, pointing to Zuckerman’s 1950s work as the final word on whether ovaries can create new egg cells. There’s another difficulty here, too—one that isn’t about biology at all, but about how scientific communities behave.

Evelyn Telfer, chair of reproductive biology at the University of Edinburgh, says that once a consensus forms, it’s hard to overturn. “You’re part of a community, and that community holds these views, and if you’re going against those views, it’s difficult to get funding,” she says.

Telfer was initially cautious about Tilly’s findings. But after collaborating with him on research using human ovarian tissue. she has become convinced that cells exist within adult ovaries and can. under certain circumstances. develop into oocyte-like structures. “These cells underwent a transformation within the tissue,” she says. “They formed what appeared to be follicles,” or small, fluid-filled sacs inside ovaries where eggs develop.

Even among those who think the cells are real, the next question is sharper: if OSCs exist, what can they actually do?

Aaron Hsueh. a professor of obstetrics and gynecology at Stanford University School of Medicine. says Tilly’s methods of using proprietary antibodies to prove these oocyte-forming cells exist are suspect. “I’m not completely against this idea [of ovarian stem cells], but I’m against Tilly’s approach,” Hsueh said.

Tilly, in turn, says his antibodies are available from a commercial vendor. He also says Hsueh “cherrypicked studies to support his ideas” and “ignores the fact that nearly 100 peer-reviewed papers have been published by numerous labs around the world supporting the existence of OSCs and/or the occurrence of postnatal oocyte formation during adulthood since our initial 2004 Nature paper.”.

Telfer’s concern is less about whether OSCs exist and more about whether they can produce viable human eggs. In her view, that ability remains unclear.

Taken together, the debate is changing the landscape even for researchers who remain skeptical. For decades, menopause has been framed as the inevitable exhaustion of a fixed egg supply. If the biology is instead more flexible—if egg production can sometimes occur later in life—then the mechanics of reproductive aging may be less static than scientists once believed.

The stakes are obvious. Tilly says adult-generated oocytes could lead to treatments for infertility. He also hopes such OSCs could restore ovarian function in cancer patients—and, one day, treat symptoms of menopause or delay it, extending women’s health span.

But the ovary isn’t a single-purpose device for making eggs. “The ovary’s not just about the eggs,” Telfer points out.

Eggs sit inside follicles, and those follicles depend on surrounding somatic (non-reproductive) cells that produce hormones and regulate egg development. As the ovaries age. those tissues become “increasingly fibrotic and mechanically altered. ” according to Telfer. potentially disrupting the signals needed for OSCs to function properly.

Tilly compares the ovary to a house and stem cells to its inhabitants. The stem cells, he says, may be present long after menopause, but “the house has fallen into disrepair,” he says. “The environment [the cells] exist in doesn’t function appropriately anymore to support their activity.”

That framing matters because it shifts the target. The challenge may not only be finding stem cells that persist; it may be repairing the environment that lets them work.

Tilly’s lab is now exploring platforms to grow engineered ovarian tissue. These “organoids” contain both a patient’s own OSCs and hormone-producing support cells. Tilly says the initial goal isn’t to produce babies, but to restore natural hormone function in people who have lost it.

The concept is straightforward. even if the biology is not: scientists could one day take and store a person’s OSCs before or after menopause. grow them as organoids outside the body. and reimplant the tissue when needed. Tilly says the organoids wouldn’t have to be placed back into the ovary itself; they could be implanted elsewhere. such as in the arm.

The hope is that the reimplanted tissue would restore natural hormone production as an alternative for hormone replacement therapy. Tilly notes that hormone replacement therapy can carry unwanted side effects and isn’t always effective, and it isn’t recommended for some people.

Tilly’s team has isolated “dormant” OSCs from ovarian tissue donated by women decades after menopause. though he says that work hasn’t yet been published. He also wants to investigate whether OSCs from women who have already gone through menopause can be “woken up” and coaxed to produce viable eggs again.

“This early-stage research direction, albeit preliminary, looks promising,” he says. But for all the momentum—and for all the personal weight infertility and menopause carry for millions—researchers are clear that there is still a long road from discovery to treatment.

Telfer stresses that the field is far from an approved OSC-based therapy for women. Researchers still need to determine whether lab-grown ovarian tissue implants are safe and function reliably over time. “We need to do a lot more of the basic work,” Telfer says.

If dormant regenerative cells can persist in the ways Tilly believes, they could reshape how ovarian failure is understood. Even before therapies exist. the debate itself is already forcing a reconsideration of what aging means inside the body—less as a fixed countdown. and more as something that might. at least in some circumstances. be interrupted.

ovarian stem cells oocytes menopause infertility reproductive biology oogonial stem cells follicular atresia organoids hormone replacement therapy Tilly Telfer Hsueh