Laurie Wang

Scientists are one step closer to understanding endometriosis, a common women’s health problem, thanks to new research from the Yale School of Medicine.

Endometriosis, a disease in which the tissue lining the uterus grows in other areas of women’s bodies, often causes pain, scarring and infertility. Even though the disease is relatively common — according to the National Institutes of Health, it affects between 6 and 10 percent of women — very little is understood about its underlying causes, according to authors of a recent study on the topic. In order to discover more about the effects of endometriosis on the body, Yale researchers studied mice that had endometrial tissue in different areas of their bodies. They found that the extra endometrial tissue’s distance from the uterus affected gene expression in the mice, with more distant tissue having a lesser but still pronounced effect on gene expression, regulating endometrial development during the menstrual cycle and establishing conditions necessary for embryo implantation. These results point to an understanding of endometriosis as a systemic disease with far-reaching effects on the entire body.

According to Hugh Taylor ‘83, one of the authors of the study and an Obstetrics, Gynecology and Reproductive Sciences professor at the Yale School of Medicine, the researchers aimed to see how endometriosis could have larger, systemic effects.

“Could there be a signal that comes from endometriosis that affects the uterus and all the other areas people complain about? Is this really a systemic disease that has far-reaching manifestations, or is, as traditionally thought, this just a local disease?” Taylor asked.

Researchers created endometriosis in two different groups of young mice. In the first group, they introduced endometrial tissue close to the uterus, creating “proximal endometriosis.” In the second group, researchers inserted the tissue farther away, creating “distal-site endometriosis.” Researchers waited three months and then examined the uteri from the mice, extracting RNA to get a better understanding of how the different types of endometriosis affected the mice’s gene expression. Although mice with proximal endometriosis had more dramatic decreases in gene expression than did mice with distal-site endometriosis, both groups of mice demonstrated decreased expression in progesterone receptors compared to the control group. Progesterone is one of the hormones that plays an important role in conception and pregnancy, Taylor said.

The researchers’ findings suggest that endometriosis is a systemic disease, according to Taylor. Although distal-site endometriosis affected gene expression less than proximal endometriosis did, it still changed how the body operated, the researchers said. Furthermore, both forms of endometriosis affected progesterone receptors, meaning that this gene is likely regulated at least in part by systemic signals — far-reaching signals that affect the entire body, Taylor said. The whole-body inflammation induced by endometriosis of both forms likely plays into this.

Yet another complicating factor is that endometrial tissue throughout the body can soak up the body’s low levels of circulating stem cells, keeping them from reaching the endometrial tissue lining the uterus, according to the paper. This lack of stem cells traveling to the uterus could prevent repair within the uterus, further contributing to the altered gene expression the researchers observed in mice, according to the study.

Ramana Mamillapalli, one of the authors of the study and a researcher at the School of Medicine, said that the typical symptoms of endometriosis include pelvic pain, painful periods with excessive bleeding, infertility and pain during intercourse.

The study points both toward further research and towards potential future cures, Mamillapalli said.

“Understanding the cellular and molecular mechanisms that are influencing systemic alterations may allow for a better understanding of the totality of this disease as well as allow for novel targeted therapies including stem cells,” Mamillapalli said.

According to the Centers for Disease Control and Prevention, the first sign of endometriosis for many women may be trouble getting pregnant.