Jiyoon Park

Researchers in the Yale School of Medicine’s Department of Obstetrics, Gynecology and Reproductive Sciences have made a key finding about endometriosis in humans and mice that could lead to new nonhormonal treatments for the disease.

“Endometriosis is caused by translocation of the endometrial tissue from the uterus of women into the peritoneal cavity, or the abdomen, during menstrual cycles,” said corresponding author Ramanaiah Mamillapalli, a research scientist at the School of Medicine. The researchers’ study was published on March 27 in the journal Reproductive Sciences.

Mamillapalli explained that endometriosis is a gynecologic disease in women between the reproductive ages of 20 and 40, in which tissues of cells released from the uterus move to the abdomen and grow lesions. The disease causes inflammation and pain in the stomach, as well as depression, anxiety and infertility.

The research team discovered that mice and people with endometriosis overproduce a specific type of receptor protein. According to Mamillapalli, the chemokine G-protein-coupled receptor CXCR7, rarely detected in normal conditions, is expressed in large quantities on cell membranes in endometriotic lesions in both mice and humans. This specific receptor signals to the cell’s nucleus to develop more cells, so that the lesions ultimately become bigger. Inhibition of this receptor can therefore stop the cell proliferation, lesion growth and inflammation and pain associated with the disease.

“We found out an overexpression of this G-protein-coupled receptor CXCR7 in endometriosis patients,” Mamillapalli said. “Then we looked at what its function in mice is, and we found that it enhanced the proliferation of cells that cause cell division. It also affects apoptosis or cell death. So it will inhibit the cell death. And then we are communicating one more manuscript in which we inhibited this molecule, and there, you can see the lesion size reduced very much.”

According to Reshef Tal, assistant professor of obstetrics, gynecology and reproductive sciences at the medical school and co-author of the paper, the study contributes to a better understanding of the pathogenesis and underlying causes of endometriosis.

“There’s still much work to do in terms of our understanding of the [endometriosis] pathogenesis, but we’re making progress and I can definitely foresee new biological therapies to combat this disease,” Tal said.

Mamillapalli said that he and researchers are now developing diagnostic tools to detect endometriosis through microRNAs, or small molecules that regulate the expression of genes like the one that encodes CXCR7. Endometriotic lesions release specific microRNAs into the bloodstream, so diagnosis of endometriosis is possible by taking someone’s blood, collecting the serum and observing the level of microRNAs present. Once the diagnosis is complete, the receptor CXCR7 can then be inhibited to treat endometriosis.

This represents significant progress, since there are no diagnostic tools on the market to detect endometriosis, said Mamillapalli, and it can take years for women to feel the symptoms of the disease. Endometriosis can be treated by surgically removing the lesions or through hormone treatments, but researchers are now in the process of developing nonhormonal treatments.

Hugh Taylor ’83, a co-author of the study and a professor in obstetrics, gynecology and reproductive sciences, said that blocking the receptor CXCR7 shows that endometriosis can be treated, raising the possibility of a novel treatment for the disease.

Taylor emphasized the importance of developing a nonhormonal treatment, since hormone treatments cause widespread changes in the body and can have multiple side effects, including mood changes, depression and bloating. Standard treatment can even involve stopping the production of all reproductive hormones, essentially causing a menopause.

“Hormonal treatments are just overpowering and try to dramatically alter hormones to abnormal levels rather than resetting things back to normal,” Taylor said.

Nonhormonal treatments, on the other hand, have the advantage of specifically targeting the lesion.

Eui Young Kim | euiyoung.kim@yale.edu