Hidden Immune Cells May Hold Key to Tackling Female Infertility

University of Manchester scientists have uncovered a hidden role for immune cells in the womb, opening the door to new treatments for infertility, miscarriage and other reproductive conditions that affect millions of women worldwide.

The findings are a breakthrough in our understanding of women's reproductive biology, one of the most under-researched areas of medicine, despite infertility and pregnancy complications affecting millions of families.

The researchers hope their findings will accelerate efforts to develop targeted therapies for a range of conditions in urgent need of advancement, including recurrent miscarriage, IVF implantation failure, uterine fibrosis (scarring) and non-cancerous growths in the womb called fibroids.

Using mouse models and samples from women, specialized white blood cells called monocytes, they found, play a vital role in keeping the uterus healthy throughout the menstrual cycle.

Their findings, published in Nature Immunology today, reveal that these cells manage inflammation, repair tissue and maintain the womb lining, challenging long-held assumptions about how the uterus regulates itself.

They showed that during a healthy menstrual cycle, large numbers of monocytes move from the bloodstream into the uterus at specific times each month.

Once there, they are able to promote inflammation when needed or help repair and rebuild tissue.

Monocytes, they add, are essential for normal tissue turnover in the womb, though when missing, the uterus developed abnormal tissue structures and scarring causing problems with reproduction, with the mice having fewer pups per litter.

Using mouse models to track how immune cells in the womb develop over time, they determined that once recruited to the womb, monocytes turn into two different types of specialized immune cells (macrophages), one causing inflammation and one promoting tissue repair.

The findings were particularly striking in women with Asherman Syndrome, an often undetected condition in which scar tissue forms inside the uterus and can cause infertility, recurrent miscarriage and pregnancy complications.

The team discovered unusually high numbers of inflammatory monocytes in women affected by Asherman’s syndrome. Rather than rising and falling naturally throughout the menstrual cycle, the cells remained persistently elevated and clustered around specialized glands in the lining of the womb.

The study suggests this abnormal immune activity in mice may contribute to the development of fibrosis and scarring inside the uterus.

The work could help identify new treatment strategies, such as blocking inflammatory pathways or targeting molecules that control the movement and behavior of monocytes, which aim to restore a healthy immune balance in the womb.

For many years we have known surprisingly little about the immune cells that live and work within the uterus. Our study shows that one type of immune cell - monocytes - are not simply bystanders but essential for maintaining a healthy womb. When their behavior becomes disrupted, normal tissue repair processes can go wrong and scarring may develop."

Dr. Lizzie Mann, Senior Author, The University of Manchester

She added: "We hope these findings will pave the way for new treatments that improve fertility and reproductive health for women affected by inflammatory womb conditions."

"The lack of knowledge in this area reflects the historic underfunding and low prioritization of women’s health."

"One critical consequence of this is the dramatic decline in global fertility rates, set to transform global population patterns."