Women may be losing their ability to produce healthy eggs later in life due to excessive scarring – or fibrosis - and inflammation in their ovaries, according to a study in mice published today in Reproduction. These findings could pave the way for new treatments that delay ovarian ageing.
Age is the most important factor in female infertility, and older mothers (aged 35+) are more likely to suffer from miscarriages and have a higher chance of embryos with chromosomal abnormalities or children with birth defects. As women worldwide delay motherhood, research into the mechanisms underlying reproductive ageing is increasingly needed.
One of the main conditions linked to ageing organs is excessive scarring which causes the accumulation of connective tissue. This condition, commonly known as fibrosis, occurs when tissues do not regenerate or heal properly. Fibrosis interferes with normal tissue function and has been previously linked to ageing in the heart, liver and kidneys.
In this study, researchers analysed ovarian tissue from populations of reproductively “young” (equivalent to women in their early twenties) and “old” mice (equivalent to women ages 38-45). They consistently identified fibrosis in the reproductively “old” mice. This age period is associated with a decline in reproductive function and egg quality in both humans and mice, raising the question of whether fibrosis in the ovaries impacts the growth and development of healthy eggs. In some reproductively “old” mice, up to 35% of the ovarian tissue was fibrotic.
Researchers also found a type of immune cell (multinucleated macrophage giant cells) in the ovaries of reproductively “old” mice only. When found in other tissues, these cells are associated with chronic inflammation, which can also contribute to tissue damage.
“The majority of reproductive aging research is focused on the eggs themselves and trying to understand why their number and quality deteriorate,” said Dr. Francesca E. Duncan, currently the Executive Director of the Center for Reproductive Science at the Northwestern University Feinberg School of Medicine. She led this study while an Assistant Professor in the Department of Anatomy and Cell Biology at the University of Kansas Medical Center. “In this study we took a different angle and instead examined the changes that occur in the environment in which the eggs develop.”
“Our work establishes fibrosis and inflammation as hallmarks of the ageing ovary and lays the foundation for considering the use of anti-fibrotic or anti-inflammatory treatments to delay or counteract the impact of reproductive ageing. This has wider implications for women’s health because ovarian fibrosis is a key feature of Polycystic Ovarian Syndrome (PCOS) and is also an unintended consequence of medical interventions such as chemotherapy and radiation,” Duncan remarked.
The research team is currently investigating how to therapeutically target the ovarian environment to improve reproductive function.