Hilde Jørgensen1, Peter Fedorcsak2, Keith Isaacson3, Erin Tevonian4, Amy Xiao4, Michael Beste5, Erik Qvigstad2, Douglas Lauffenburger6, Linda Griffith7. 1. Department of Gynecology, Oslo University Hospital, Ullevål, Norway. 2. Department of Gynecology, Oslo University Hospital, Ullevål, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway. 3. Newton-Wellesley Hospital and Harvard Medical School, Boston, Massachusetts. 4. Biological Engineering Department. 5. Biological Engineering Department; Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. 6. Biological Engineering Department; Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, Massachusetts; Biology Department, Massachusetts Institute of Technology, Cambridge, Massachusetts. 7. Biological Engineering Department; Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. Electronic address: griff@mit.edu.
Abstract
OBJECTIVE: To evaluate whether endometrial molecular profiles distinguish subsets of patients according to clinical characteristics, and to infer dysregulated immune networks, by measuring cytokines, chemokines, and growth factors in endometrial biopsy specimens from a cohort of infertile women with a high incidence of endometriosis. DESIGN: Prospective cohort study. SETTING: Department of Gynecology at a university hospital. PATIENT(S): Patients undergoing laparoscopy for infertility assessment (n = 103). INTERVENTION(S): Endometrial biopsies were performed during surgery. Fertility outcome and clinical parameters were registered preoperatively and after 6 months. MAIN OUTCOME MEASURE(S): The concentrations of 48 factors in endometrial biopsy specimens were analyzed with respect to clinical status in univariate and multivariate frameworks. RESULT(S): The concentrations of 44 factors from endometrial tissues of 74 patients were suitable for analysis. Although the tissue concentrations of interleukin (IL)15, IL-7, and interferon γ-induced protein (IP)-10 were individually lower in patients with endometriosis than in those without endometriosis, the differences were not significant after multiple comparison. However, multivariate modeling incorporating covariation showed separation between subsets of endometriotic and nonendometriotic patients, based predominantly on IP-10, monocyte chemoattractant protein-1, IL-16, and IL-18; this result was independent of cycle and fertility status. Analysis restricted to endometrial tissues from the secretory phase separated endometriotic and nonendometriotic patients by a combination of IL-15, IP-10, monocyte chemoattractant protein-1, IL-16, and IL-18. This combination suggests a uterine natural killer cell defect. We found no significant correlations between endometrial cytokines and fertility outcome. CONCLUSION(S): A molecular signature in endometrial tissue was able to distinguish endometriotic from nonendometriotic patients, implicating uterine natural killer cells in endometriosis.
OBJECTIVE: To evaluate whether endometrial molecular profiles distinguish subsets of patients according to clinical characteristics, and to infer dysregulated immune networks, by measuring cytokines, chemokines, and growth factors in endometrial biopsy specimens from a cohort of infertile women with a high incidence of endometriosis. DESIGN: Prospective cohort study. SETTING: Department of Gynecology at a university hospital. PATIENT(S): Patients undergoing laparoscopy for infertility assessment (n = 103). INTERVENTION(S): Endometrial biopsies were performed during surgery. Fertility outcome and clinical parameters were registered preoperatively and after 6 months. MAIN OUTCOME MEASURE(S): The concentrations of 48 factors in endometrial biopsy specimens were analyzed with respect to clinical status in univariate and multivariate frameworks. RESULT(S): The concentrations of 44 factors from endometrial tissues of 74 patients were suitable for analysis. Although the tissue concentrations of interleukin (IL)15, IL-7, and interferon γ-induced protein (IP)-10 were individually lower in patients with endometriosis than in those without endometriosis, the differences were not significant after multiple comparison. However, multivariate modeling incorporating covariation showed separation between subsets of endometriotic and nonendometriotic patients, based predominantly on IP-10, monocyte chemoattractant protein-1, IL-16, and IL-18; this result was independent of cycle and fertility status. Analysis restricted to endometrial tissues from the secretory phase separated endometriotic and nonendometriotic patients by a combination of IL-15, IP-10, monocyte chemoattractant protein-1, IL-16, and IL-18. This combination suggests a uterine natural killer cell defect. We found no significant correlations between endometrial cytokines and fertility outcome. CONCLUSION(S): A molecular signature in endometrial tissue was able to distinguish endometriotic from nonendometriotic patients, implicating uterine natural killer cells in endometriosis.
Authors: Andrew J Shih; Robert P Adelson; Himanshu Vashistha; Houman Khalili; Ashima Nayyar; Radha Puran; Rixsi Herrera; Prodyot K Chatterjee; Annette T Lee; Alexander M Truskinovsky; Kristine Elmaliki; Margaret DeFranco; Christine N Metz; Peter K Gregersen Journal: BMC Med Date: 2022-09-15 Impact factor: 11.150