A new study suggests that endometriosis is a systemic disease with widespread manifestations, such as altered gene expression, even when located far from the uterus. The research paper, entitled “Endometriosis Located Proximal to or Remote From the Uterus Differentially Affects Uterine Gene Expression,” and published in Reproductive Sciences, challenges previous believes of endometriosis as a local peritoneal disease.
This study aimed to unveil some of the molecular mechanisms at play, as proposed in a press release by one of its authors, Dr. Hugh Taylor, an Obstetrics, Gynecology and Reproductive Sciences professor at the Yale School of Medicine: “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?”
Researchers at Yale School Medicine studied two animal models of endometriosis to understand the bodily effects of endometriosis and, specifically, whether the proximity of endometrial lesions to the uterus had any influence on the altered gene expression. The first mouse model had endometrial tissue introduced in the peritoneal cavity, close to the uterus (proximal endometriosis), while in the second mouse model this tissue was introduced far from the uterus, creating a distal endometriosis. After three months, uterine tissue was analysed and gene expression in the uterus of both models evaluated.
Results showed that although mice with distal endometriosis had a less pronounced decrease in gene expression, both models were affected and showed decreased expression in several genes related to endometrial receptivity in the uterine tissue. Moreover, both models had a lower expression of progesterone receptors, leading researchers to hypothesize this gene could be controlled by signals sent from further regions in the body. Progesterone is a hormone of great importance in the establishment and maintenance of pregnancy. In addition, endometrial tissue keeps circulating stem cells from reaching the lining of the uterus, a factor that might hinder repair in this location and contribute for the decreased gene expression levels observed.
The results suggest that even remote disease can selectively alter gene expression, an effect that seems to be related to lesions’ distance from the uterus. This novel information significantly contributes to the understanding of the mechanisms underlying endometriosis, demonstrating for the first time that the condition has a widespread effect on the body, and may allow the identification of new therapy targets.