Project description:Endometriosis is a common, chronic inflammatory condition that frequently results in pain and infertility and is estimated to affect 6–10% of women of reproductive age. However, the mechanisms underlying the induction of inflammation in endometriosis remain unclear. Here, we identified that ectopic endometrial T-cell-derived active interleukin (IL)-16 acts as an inflammation-driving cytokine in endometriosis. Furthermore, we found that in ectopic endometrial T cells, the activation of IL-16 requires iron overload-induced caspase-3 activity and that the release of active IL-16 is reliant on GSDME-mediated pyroptosis. These observations suggest that active IL-16 may represent a promising target in the treatment of endometriosis.
Project description:We performed gene expression analysis human peritoneal endometriosis lesions, eutopic endometrium from endometriosis patients and peritoneum form endometriosis patients.The goal of the study was to analyse gene expression differences between peritoneal endometriosis lesion and eutopic endometrium and peritoneal endometriosis lesion and peritoneum.
Project description:This project aims at comparing endometrium from women with and without endometriosis during the secretory phase of menstrual cycle. The present results constitute a first step towards identifying potential diagnosis biomarkers and may provide a better understanding of endometriosis especially the etiology of the disease.
Project description:Mechanisms of immune dysregulation against established tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear cell ovarian tumors may partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here the most comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC). RNA was extracted from 120 paraffin tissue blocks comprising of normal endometrium (n=32), benign endometriosis (n=30), atypical endometriosis (n=15) and EAOC (n=43). Serous tumors (n=15) were included as non-endometriosis associated controls. The immune microenvironment was profiled using Nanostring and the nCounter® GX Human Immunology Kit, comprising probes for a total of 511 immune genes. Please note that 3 normal endometrium samples did not pass the array quality filtering and therefore excluded in the data analyses.
Project description:Endometriosis is a gynaecological disease facing significant diagnostic challenges, contributing to an extensive diagnostic delay. Non-invasive diagnostic biomarkers of endometriosis could expedite diagnosis and minimise the reliance on surgery to confirm endometriosis. This pilot study aimed to identify candidate protein biomarkers of endometriosis from cervicovaginal fluid i) collected from consenting people having surgery for suspected endometriosis and ii) sampled via low vaginal swab. Samples from people with (n=20) and without (n=19) endometriosis across were analysed by data independent acquisition mass spectrometry using the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH)-MS approach. Samples were measured and analysed in two experimental runs (E1 and E2) based on time periods of sample collection. ELISA was performed to validate SWATH-MS findings.
Project description:Background. Endometriosis is a common, complex disorder which is underrecognized and subject to prolonged delays in diagnosis. It is accompanied by significant changes in the eutopic endometrial lining. Methods . We have undertaken the first single cell RNA-sequencing (scRNA-Seq) comparison of endometrial tissues in freshly collected menstrual effluent (ME) from 33 subjects, including confirmed endometriosis patients (cases) and controls as well as symptomatic subjects (who have chronic symptoms of endometriosis but have not been diagnosed). Results . We identify a unique subcluster of proliferating uterine natural killer (uNK) cells in ME-tissues from controls that is almost absent from endometriosis cases, along with a striking reduction of total uNK cells in the ME of cases (p<10 -16 ). In addition, an IGFBP1+ decidualized subset of endometrial stromal cells are abundant in the shed endometrium of controls when compared to cases (p<10 -16 ) confirming findings of compromised decidualization of cultured stromal cells from cases. By contrast, endometrial stromal cells from cases are enriched in cells expressing pro-inflammatory and senescent phenotypes. An enrichment of B cells in the cases (p=5.8 x 10 -6 ) raises the possibility that some may have chronic endometritis, a disorder which predisposes to endometriosis. Conclusions . We propose that characterization of endometrial tissues in ME will provide an effective screening tool for identifying endometriosis in patients with chronic symptoms suggestive of this disorder. This constitutes a major advance, since delayed diagnosis for many years is a major clinical problem in the evaluation of these patients. Comprehensive analysis of ME is expected to lead to new diagnostic and therapeutic approaches to endometriosis and other associated reproductive disorders such as female infertility.
Project description:Endometriosis is a complex pathological condition in which multiple components are involved in the disease development and clinical outcome. Endometriosis is mainly an inflammatory codition estrogen-dependent, with unknown pathogenesis, that is characterized by dissemination of edometrium tissue in ectopic position (ovary or pelvic peritoneum). Two main theories rise the pathologic onset: the presence of retrograde menstruation and celomic metaplasia in the pelvic peritoneum, that can occur for development defects. Endometriosis is related not only to genetic or immunological changes and to environmental pollution factors, as the endocrine interferents. The disease phenotype results from multiple events (genetics and enviromental), thus it is difficult to find a single gene as causative while is more probable that a gene network/s might involved in the onset and mantainement of the disease state. The peculiarity of endometriosis rely on the tissue speificity manteinance in the ectopic position, where it responds to the hormone stimuli as the tissue in the eutopic position. In order to identify genes potentially involved in growth and mainteinance of the ectopic endometrium, we have profiled ectopic (8 samples) and eutopic endometrium (8 samples) from several affected woman in the proliferative phase. As control we used endometrium from normal health donors in the same phase (6 samples).
Project description:We primary cultured ectopic endometrial cells from patients with endometriosis (2 cases) and without endometriosis(2 cases) and collected cell culture supernatants(P0). We isolated exosomes from cell culture supernatants by differential centrifugation and then performed proteome analysis on the two groups of exosomes to investigate the role of ectopic endometrial cell-derived exosomes in the development of endometriosis.
Project description:Endometriosis is a common disease seen by gynecologists. Clinical features involve pelvic pain and unexplained infertility. Although endometriosis is pathologically characterized by endometrial tissue outside the normal uterine location, endometriosis is otherwise not easily explained. Endometriomas, endometriotic cysts of the ovary, typically cause pain and distortion of pelvic anatomy. To begin to understand the pathogenesis of endometriomas, we carried out transcriptome:microRNAome analysis of endometriomas and eutopic endometrium, using gene expression arrays and next generation small RNA sequencing technology. Keywords: two group comparison Patients undergoing surgery for endometriomas, suspected endometriosis, pelvic pain, abnormal uterine bleeding, pelvic organ prolapse, or uterine leiomyomas were approached for participation. After informed consent, the patients underwent scheduled surgical procedure. Tissues were collected either as cyst wall of endometrioma or endometrial curettage of hysterectomy specimen and placed directly into RNALater (Ambion, Austin, TX) and eventually frozen at -80?C. Samples were designated as endometriomas or non-endometriosis control endometrium based on surgical pathology reports. Total RNA was isolated from frozen tissue. High quality RNA was subjected to Illumina’s Human WG-6 version 2.0 BeadChips (Illumina). . *** This Series represents the transcriptome component of the study. ***