September 06, 2016
By Kay Hawes
Research led by investigators at the University of Kansas Medical Center shows that women may be losing their ability to produce healthy eggs later in life due to excessive scarring and inflammation in their ovaries. The study in mice was published this month in Reproduction. These findings could pave the way for new treatments that delay ovarian aging.
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, more research into the mechanisms underlying reproductive aging is needed.
One of the main conditions linked to aging 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 aging in the heart, liver and kidneys.
"The majority of reproductive aging research is focused on the eggs themselves and trying to understand why their number and quality deteriorate," said Francesca E. Duncan, Ph.D., currently the executive director of the Center for Reproductive Science at the Northwestern University Feinberg School of Medicine. Duncan led this study while an assistant professor in the Department of Anatomy and Cell Biology at KU 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."
Researchers analyzed 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 affects the growth and development of healthy eggs. In some reproductively "old" mice, up to 35 percent 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.
Duncan collaborated with, Michele T. Pritchard, Ph.D., assistant professor in the Department of Pharmacology, Toxicology and Therapeutics at KU Medical Center, whose research focuses on understanding mechanisms behind abnormal wound healing in the liver leading to fibrosis.
"This organic collaboration capitalized on our individual expertise to open the doors to a completely novel way to approach aging in the mammalian ovary" said Pritchard. "Our work establishes fibrosis and inflammation as hallmarks of the aging ovary," Duncan said. "And it lays the foundation for considering the use of anti-fibrotic or anti-inflammatory treatments to delay or counteract the impact of reproductive aging."
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. The research team is currently investigating how to therapeutically target the ovarian environment to improve reproductive function.