Scientists are making inroads in understanding one of the central mysteries of human reproduction: Why do women’s eggs deteriorate as they age?

The broad strokes have been well-known - the ticking of a woman’s biological clock increases risk of miscarriage and infertility, often caused by eggs with the wrong number of chromosomes, the structures that carry DNA.

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Researchers who presented their work at the Fertility 2026 conference in Edinburgh, Scotland, say they have identified how the decline of a particular protein as women age could be a clue to the problem.

Agata Zielinska, one of the authors of the study, which has not yet been peer-reviewed, is co-founder of biotech company Ovo Labs. The company is working toward launching a clinical trial that could test whether restoring that protein could improve the quality of eggs used for in vitro fertilization (IVF).

“If you want to come up with strategies to improve egg quality and develop clinical ways to actually help couples to conceive, you have to understand what’s going wrong at the molecular level,” Zielinska said.

Outside scientists cautioned that the work is a promising first step and that it is not likely to be the only explanation for chromosomal errors. But it adds to a growing body of science probing fundamental questions about the development of eggs that could lead to new options and greater success rates in human reproduction.

The mismatch between the biologically optimal window for reproduction and the societal trend toward delaying childbirth poses an anguishing challenge for many people trying to start a family.

Late last year, a separate team of scientists demonstrated in Nature Aging a way to mimic the aging process in mouse eggs, a tool that allows researchers to systematically probe the molecular failures that lead to chromosomal abnormalities - and identify ways to combat them.

“We’re quite a long way from saying reproductive aging is not that much of a problem anymore. The short-term goal would be to extend [the reproductive window] by three to five years,” said Binyam Mogessie, a professor of molecular, cellular and developmental biology at Yale University who led the Nature Aging paper and is planning to screen for drugs that could improve the viability of eggs. “It would be super consequential,” he said.

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Knowledge gaps in female reproduction

Female reproduction is full of puzzles.

Men produce sperm throughout their lives. Women, on the other hand, are born with their lifetime supply of oocytes - the precursor cells that mature into eggs. In the womb, a fetus has about 7 million of them in their ovaries, but at birth, there are only about a million left. Those oocytes that survive the attrition stay frozen in a paused state, until ovulation years or decades later.

“That of course creates great problems at the chromosome level, because they are kind of hanging out for years in humans, which is insane in some ways,” said Paula Cohen, director of the Cornell Reproductive Sciences Center.

In one of the final stages of meiosis, paired copies of chromosomes are supposed to separate in an orderly fashion, leaving an egg with one copy of each chromosome. The other half of the genetic material is discarded - “Why do they eject half their cargo?” Cohen asked “It’s very crazy.”

The problem is that during the prolonged, decades-long pause, the paired copies of chromosomes in each oocyte can separate prematurely - which then can lead to too many, or too few of them ending up in the egg. This failure in the process, referred to as chromosomal cohesion, can lead to aneuploidy - the wrong number of chromosomes in an egg - a major cause of infertility and IVF failure.

Scientists have increasingly focused on trying to unravel all the molecular steps of what goes awry with the cohesion complex. But in the new study, in mouse and human cells, Zielinska and colleagues found a dropoff in levels of the protein called Shugoshin, Japanese for “guardian spirit,” that protects the cohesion proteins that hold the chromosomes in place.

“The cohesion is more vulnerable, and the chromosomes are more likely to fall apart,” said Melina Schuh, a director at the Max Planck Institute for Multidisciplinary Sciences who led the study. Schuh also co-founded Ovo Labs and is part of the team trying to translate these insights into interventions that could improve fertility.

Michael Lampson, a biology professor at the University of Pennsylvania who was not involved in the research, said that much of the focus in the field had been on the loss as women age of proteins, called cohesin proteins, directly involved in maintaining chromosomal cohesion. The new study highlights the potential role of a different protein that guards those proteins.

“By the time you’re already 40 years old, you can’t get them back. But whatever you have left, it does sort of make sense that if you don’t have many cohesin proteins left, you have to do a good job protecting the ones you have,” Lampson said.

When the scientists restored production of the protein by microinjecting mRNA that coded for the protective Shugoshin protein, they found that they were able to increase the number of eggs that had chromosomes that weren’t prematurely coming apart- from about half of the eggs to nearly three quarters.

“They see a partial rescue. That tells you there is a contribution,” Mogessie said. He added that further work would also have to show whether increasing the production of the protein would really reverse a loss of cohesion that already occurred with aging, or would simply protect the egg against the future effects of aging.

Cohen agreed that while efforts to increase cohesion between chromosomes is a worthy target, it won’t solve the problem for every woman trying to pregnant.

“We don’t know all the answers. If cohesion is critical, and we can repair cohesion in a large number of women, then we can improve their chances of having a successful pregnancy,” Cohen said. “That won’t solve everybody’s problem ... but we’re so much further than even 10 years ago.”

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