A new study from Northwestern Medicine reveals that women’s decreasing ability to produce healthy eggs as they age might be caused by excessive scarring and inflammation in their ovaries. The research, conducted on mice, is the first to show that the ovarian environment itself ages—and this aging impacts the quality of eggs produced.
Most research on female fertility has focused directly on the eggs, exploring why their number and quality drop as women enter their forties. Poor egg quality is linked to infertility, miscarriages, and birth defects. However, this study took a different approach by examining the ovarian stroma—the tissue environment where eggs develop. Scientists have long known that a cell’s environment influences its growth and function, but little was understood about how the ovarian stroma changes with age.
Francesca Duncan, the study’s lead author and executive director of the Center for Reproductive Science at Northwestern University Feinberg School of Medicine, explained, “Eggs from young and old animals may look the same under a microscope, but the environment where they grow is very different. Ovaries from older mice show signs of fibrosis and inflammation. This unhealthy environment likely contributes to the eggs’ reduced quality.”
The study will be published on August 5 in the journal Reproduction. Duncan conducted the research while at the University of Kansas Medical Center.
Researchers analyzed ovarian tissue from young mice (equivalent to women in their early twenties) and old mice (equivalent to women aged 38-45). They consistently found fibrosis—thick, scar-like tissue—in the older mice’s ovaries. This age range corresponds to a natural decline in reproductive function in both humans and mice. In some older mice, up to 35% of ovarian tissue was fibrotic.
The team also discovered special immune cells called multinucleated macrophage giant cells only in the ovaries of older mice. These cells are known to promote chronic inflammation when present in other tissues. In addition, genes and proteins linked to inflammation were more active in ovaries from the older group.
“Our research identifies fibrosis and inflammation as key signs of ovarian aging,” said Duncan, who is also an associate research professor in obstetrics and gynecology at Feinberg. “This opens the door to exploring anti-fibrotic or anti-inflammatory treatments that might delay or reduce the effects of reproductive aging.”
Duncan pointed out that the egg’s growth environment is complex and often overlooked. “No one has studied deeply how this environment changes with age. It’s an important but underappreciated area,” she said.
These findings have implications beyond natural aging. Ovarian fibrosis is also a feature of polycystic ovary syndrome (PCOS), a common hormonal disorder in women of reproductive age. Additionally, fibrosis can result from chemotherapy and radiation treatments.
Currently, Duncan’s team is investigating ways to target the ovarian environment with therapies to improve reproductive health and fertility.
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