The Biological Dogma That Women Don’t Make New Eggs After Birth May Be Wrong

For nan past 70 years scientists person taught america that female mammals are calved pinch a finite ovarian ovum supply, and that this reserve steadily declines complete nan lifespan. In humans, that proviso dwindles until menopause, erstwhile it goes bankrupt.

Yet a increasing assemblage of investigation is challenging that dogma. Over nan past 2 decades, scientists person identified cells successful nan big ovaries of mice, cows, pigs, non-human primates and humans that, nether definite conditions, look tin of generating caller immature ovum cells, known arsenic oocytes. They aren’t definite whether these cells tin nutrient viable eggs. Nevertheless, nan findings are fueling a contentious statement successful reproductive biology and raise a provocative, and controversial, possibility: Ovarian aging whitethorn beryllium acold much move than we thought—and possibly moreover reversible.

“Previous to this work, each consequence to questions astir infertility aliases menopause was rooted successful nan conception that women only person a fixed number of eggs to activity with,” says Jonathan Tilly, a biologist astatine Northeastern University. “But what if that wasn’t nan case?”

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A New Understanding of nan Ovaries

Scientists first projected nan thought that ovaries mightiness make caller eggs done life arsenic early arsenic nan 1920s. The thought mislaid steam aft influential activity successful nan mid-20th period by British intelligence Solly Zuckerman, who counted oocytes successful animals astatine different life stages. He didn’t observe nan statement of immoderate caller oocytes during his experiments and truthful concluded that ovaries conscionable couldn’t make caller cells.

His conclusion went unchallenged until 2004, erstwhile Tilly and his squad published a insubstantial successful Nature arguing that nan “fixed ovum pool” thought didn’t adhd up mathematically. The logic why has to do pinch a process called follicular atresia—the earthy degeneration and decease of oocytes earlier they tin perchance go a mature egg. But nan complaint astatine which oocytes died disconnected seemed inconsistent pinch nan number that remained later successful life. This discrepancy “pointed to nan thought that location must beryllium immoderate benignant of caller ovum accumulation happening,” Tilly says.

Tilly projected that specialized stem cells, called oogonial stem cells, aliases OSCs, must beryllium producing caller oocytes—just arsenic spermatogonial cells proceed to make sperm successful testes. Stem cells are rare, unspecialized cells that tin go a assortment of compartment types. They are incredibly useful for bodily repair and regeneration.

In 2009, researchers from Shanghai Jiao Tong University successfully isolated OSCs from big mice and studied their oocyte-forming ability. Then, successful 2012, Tilly and others showed nan cells could beryllium recovered in big quality ovaries.

In 2017, Tilly’s squad utilized a familial instrumentality to technologist female mice truthful that immoderate recently formed oocytes would glow fluorescent greenish nether a microscope. The findings suggested that not only do newly generated oocytes support adding caller eggs to nan mice’s ovarian reserve, but besides that those caller cells could beryllium utilized to nutrient viable rodent offspring. In 2023, Tilly's squad reported that while OSCs persist into aged property successful mice, they look to suffer their expertise to make caller oocytes arsenic cardinal developmental genes go inactive—a shape that was besides seen successful quality ovarian insubstantial and whitethorn explicate why OSCs still beryllium post-menopause.

Some scientists dainty nan full thought of OSCs pinch fierce skepticism. They deliberation Zuckerman’s activity successful nan 1950s stands arsenic nan last connection connected whether nan ovaries tin create caller ovum cells.

Evelyn Telfer, chair of reproductive biology astatine nan University of Edinburgh, notes that a technological consensus, erstwhile formed, are difficult to overturn. “You’re portion of a community, and that organization holds these views, and if you’re going against those views, it’s difficult to get funding,” she says.

Telfer herself was initially cautious astir Tilly’s findings. But aft collaborating pinch him connected investigation utilizing quality ovarian tissue, she has go convinced that cells beryllium wrong big ovaries, and can, nether definite circumstances, create into oocyte-like structures. “These cells underwent a translator wrong nan tissue,” she says. “They formed what appeared to beryllium follicles,” aliases small, fluid-filled sacs wrong ovaries wherever eggs develop.

Some scientists still person doubts astir whether OSCs exist. But, Telfer says, galore person turned to nan adjacent question: If they exist, what tin they do?

Aaron Hsueh, a professor of obstetrics and gynecology astatine Stanford University School of Medicine, says Tilly’s methods of utilizing proprietary antibodies to beryllium these oocyte-forming cells beryllium are suspect. “I’m not wholly against this thought [of ovarian stem cells], but I'm against Tilly’s approach,” Hsueh said. Tilly says that his antibodies are disposable from a commercialized vendor, that Hsueh cherrypicked studies to support his ideas and “ignores nan truth that astir 100 peer-reviewed papers person been published by galore labs astir nan world supporting nan beingness of OSCs and/or nan occurrence of postnatal oocyte statement during adulthood since our first 2004 Nature paper.”

For her part, Telfer says that while she is judge OSCs exist, it’s unclear whether they tin nutrient viable quality eggs.

Ultimately, nan subject is reshaping really immoderate researchers deliberation astir nan ovary itself. For decades, menopause has been viewed arsenic nan inevitable exhaustion of a fixed ovum supply. But if that tin beryllium halted aliases reversed, nan biology of reproductive aging whitethorn beryllium acold little fixed than scientists erstwhile believed.

Eggs Are Part of a Larger System

Adult-generated oocytes could lead to treatments for infertility, Tilly says. He besides hopes specified OSCs could reconstruct ovarian usability successful crab patients—and 1 time dainty symptoms of menopause aliases moreover hold it, extending women’s wellness span. The ovaries are analyzable systems, however, and it’s conscionable not known if making caller eggs would person those effects. “The ovary’s not conscionable astir nan eggs,” Telfer points out.

Eggs do not beryllium successful isolation; they are housed wrong follicles and supported by surrounding somatic (non-reproductive) cells that nutrient hormones and modulate ovum development. As nan ovaries age, those tissues go “increasingly fibrotic and mechanically altered,” according to Telfer, perchance disrupting nan signals needed for OSCs to usability properly.

Tilly compares nan ovary to a location and nan stem cells to its inhabitants. The stem cells, he says, whitethorn beryllium coming agelong aft menopause, but “the location has fallen into disrepair,” he says. “The situation [the cells] beryllium successful doesn’t usability appropriately anymore to support their activity.”

But possibly nan “house” isn’t ever necessary. Tilly’s laboratory is moving connected platforms to turn engineered ovarian tissue; these “organoids” incorporate some a patient’s ain OSCs and hormone-producing support cells. The first extremity is not to nutrient babies, but alternatively to activity toward restoring earthy hormone usability successful group who person mislaid it.

Scientists could 1 time return and shop a person’s OSCs earlier aliases aft menopause, turn them arsenic organoids extracurricular nan body, and reimplant nan insubstantial erstwhile needed. The organoids would not request to beryllium placed into nan ovary itself—they could beryllium implanted successful nan arm, for example. The thought is that nan reimplanted insubstantial would reconstruct earthy hormone accumulation arsenic an replacement for hormone replacement therapy, which tin transportation unwanted broadside effects, isn’t ever effective, and isn’t recommended for immoderate people.

Tilly’s laboratory has isolated “dormant” OSCs from ovarian insubstantial donated by women decades aft menopause; but this activity has not yet been published, he says. “It really changes [our] position connected why ovaries fail,” he says. His squad besides hopes to analyse whether OSCs from women who person already gone done menopause tin beryllium “woken up” and coaxed to nutrient viable eggs again. “This early-stage investigation direction, albeit preliminary, looks promising,” he says.

As tantalizing arsenic these results are, we are a agelong measurement from an approved OSC-based therapy for women. Researchers still request to find whether nan lab-grown ovarian insubstantial implants are safe and usability reliably complete time. “We request to do a batch much of nan basal work,” Telfer says. If dormant regenerative cells tin persist however, they could style early fertility and menopause treatments.