October 16, 2019

Understanding the Role of PGE2 and CD55 in the Pathogenesis of Endometriosis May Lead to New Treatments

Study uncovers molecular pathway that may lead to formation of endometriosis

endometriosis

Cleveland Clinic researchers found that high levels of prostaglandin E2 (PGE2) may induce the formation of endometriosis through a novel pathway involving the complement regulatory protein CD55. The study will be presented at the American Society for Reproductive Medicine’s 2019 Scientific Congress and Expo, held October 14-16 in Philadelphia.

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

“Endometriosis is a complex and enigmatic disease with many factors and contributors. There almost certainly isn’t one single factor driving it, but evidence does suggest that PGE2 is critical,” states Ofer Reizes, PhD, the Laura J. Fogarty Endowed Chair for Uterine Cancer Research in Cleveland Clinic’s Lerner Research Institute and senior author on the study.

PGE2 is widely regarded as central to the pathogenesis of endometriosis. Observational studies analyzing peritoneal fluid have shown that patients with endometriosis have increased levels of PGE2 compared to healthy control women. Furthermore, treatment with drugs that diminish PGE2 have been shown to improve symptoms in humans and decrease lesion size in animal models.

PGE2 seems to alter CD55 expression levels

Investigators first localized the presence of CD55 protein in specimen from eutopic and ectopic endometrium of human pathology specimen using immunohistochemistry. They then performed CD55 expression analysis on endometrial stromal (T-HESC) and endometriotic epithelial (12Z) cell cultured in flasks and treated with increasing doses of PGE2 and determined ability of the cells to adhere to tissue culture surfaces, a necessary step for endometriosis formation.

Advertisement

“Our data suggest that CD55 has a role in the pathogenesis of endometriosis,” states Elliott Richards, MD, a fellow in Cleveland Clinic’s Ob/Gyn & Women’s Health Institute. “CD55 is an important regulator of the complement system, part of the body’s innate immune system. For decades it was thought that CD55 action was pretty much limited to complement regulation outside the cell surface. Recent studies in other diseases and organ systems, however, show that CD55 can have other functions in the cell. We investigated whether this was the case in endometriosis, since it is one of the genes misregulated in patients with the disease. We found that CD55 may play a role in cell adhesion in the early formation of endometriosis. What is most interesting is that PGE2 seems to alter CD55 expression levels, which may explain how the misregulation works.”

Dr. Richards cautions that these findings are preliminary, as this study includes only in vitro data. “Experiments using these cell lines can give clues as to what may be happening, but endometriosis lesion formation involves very complex biology. We can’t definitively say whether these processes in cell lines would happen the same way in the tissue in the body. The next step is to perform experiments in animal models. We have nearly completed these animal experiments and are in the process of analyzing the data,” Dr. Richards notes.

Toward new treatments for endometriosis

Patients with endometriosis report a lower health-related quality of life, with symptoms of chronic pelvic pain, dysmenorrhea, dyspareunia, gastrointestinal symptoms and infertility. “Endometriosis is estrogen-dependent and generally occurs between menarche and menopause. Nonsurgical treatments to date have focused on hormonal suppression,” states Jeffrey M. Goldberg, MD, Program Director for the Reproductive Endocrinology & Infertility Fellowship and a co-author on the study. “The results of this, and other ongoing studies, may provide us with a molecular pathway to better understand the pathogenesis of this disease state, with the ultimate goal of creating new non-hormonal treatment options for endometriosis.”

Advertisement

Related Articles

woman with milk and lettuce
February 14, 2024
Neighborhood Factors Affect Early Pregnancy Metabolic Health

Deprivation is linked to impaired glucose intolerance and racial disparities

23-WHI-4386458 – OGI – CQD – topical treatment for VIN
November 30, 2023
Trial Shows Promise for Topical Treatment for VIN

Artesunate ointment is safe well and tolerated patients with vulvar intraepithelial neoplasia

contraception
June 15, 2023
Update on Current Contraceptive Options

A case-based discussion of efficacy, eligibility and use

OB/GYN Residents Wellness
January 13, 2022
Wellness Efforts Are Needed by OB-GYN Residents, But One Solution Does Not Fit All

Workshop curriculum was valued by some, while others would have preferred time for themselves

Cecile Ferrando MD
June 1, 2021
Pain in Transgender Men Undergoing Hysterectomy

Study finds lower incidence of endometriosis than in cisgender patients

18-OBG-1364-DesaiAccessBlastocyst-650×450
September 23, 2020
Uninterrupted Culture in Time-Lapse Incubator Supports Human Embryonic Development

Large randomized study compares embryo growth kinetics and live birth rates between culture media

20-WHI-1938960 CQD WHI – Outcomes of Vaginoplasty Surgery – Ferrando_CQD Hero_650x450
August 27, 2020
Gender-Affirming Vaginoplasty: Reducing Complications

Surgeon experience is key to reducing adverse events

20-WHI-1878668-CQD-Predicting-Early-Pregnancy-Loss_Detti_CQD_650x450_A
April 23, 2020
Predicting Early Pregnancy Loss: Insights from Early, Serial Ultrasounds in Pregnancy

Introducing Laura Detti, MD, newly appointed Chair of the Department of Subspecialty Care for Women’s Health

Ad