Immune-inflammation gene signatures in endometriosis patients

Abstract

Objective To determine if the molecular profiles of endometriotic lesions contain informative measures of inflammation and immune dysfunction that may contribute to better understanding of the interplay between immune dysfunction and inflammation and their contribution to endometriosis pathogenesis. Design Immune and inflammation transcriptomic analysis with the use of the Nanostring nCounter GX Human Immunology V2 platform (579 human immune and inflammation–related genes and 15 housekeeping genes). Setting Academic university and teaching hospital. Intervention(s) None. Patient(s) Stage III–IV endometriosis patients with infertility (n = 8) and fertile disease-free control women undergoing tubal ligation (n = 8). Menstrual stage was matched to secretory phase in all participants. Main Outcome Measure(s) Immune and inflammation transcriptomics quantification from ectopic endometriotic lesions and matched eutopic endometrium from patients. Endometria of fertile women served as control subjects. Result(s) Our results displayed endometriotic lesions as molecularly distinct entities compared with eutopic endometrium and endometrium of control samples; 396 out of 579 screened immune and inflammation–related genes were significantly different in ectopic tissues compared with control endometrium. Most importantly, eutopic endometrium of the patients displayed a unique molecular profile compared with the control endometrium (91/579 genes were significantly different), particularly of genes involved in regulation of cell apoptosis and decidualization. Conclusion(s) We characterize differential expression of immune-inflammation genes in endometriosis patients, and show molecular distinction of eutopic endometrium of patients compared with control fertile women.

Endometrial BCL6 testing for the prediction of in vitro fertilization outcomes: a cohort study

“…Progesterone is essential for the establishment of pregnancy, so reduction in progesterone action would logically be associated with multiple down-stream changes in gene expression in the endometrium. In addition, inflammation is associated with P-resistance and an immune-regulated impact on the endometrium (39,40). BCL6 pairs with the histone deacetylase SIRT1, is centrally associated with epigenetic alterations in endometrial gene expression associated with endometriosis and likely has multiple effects on other key down-stream progesterone-regulated genes (18).…”

Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why

“…Inflammation is known to alter endometrial receptivity and has been associated specifically with endometriosis (57, 58). Endometriosis results in systemic and local cytokine expression changes that disrupts normal endometrial function (59-62), and is reversible by surgical removal of endometriosis (63). One of the hallmark changes seen in the endometrium of women with endometriosis is an induction of p450 aromatase expression (64, 65).…”

Ендометріоз Та Безпліддя

“…Прогестерон володіє протизапальною дією в умовах нормального менструального циклу, у пізню секреторну фазу зниження рівня прогестерону запускає каскад реакцій, що проявляються зниженням метаболізму простагландинів та підвищенням рівня реактивних форм кисню (АФК) та, як наслідок, індукує менструацію [26]. Порушення резистентності до прогестерону імітує пізню секреторну фазу та провокує передчасний запуск даного каскаду реакцій, накопичення медіаторів запалення та порушення регуляції апоптозу, клітинної адгезії [7,40]. За рахунок хронічного запального процесу та каскаду біохімічних реакцій у малому тазу вивільняється надмірна кількість простагландинів, що провокують утеротубальну дисперестальтику, наслідком якої є порушення транспорту гамет та ембріона [13].…”