The Eutopic Endometrium Proteome in Endometriosis Reveals Candidate Markers and Molecular Mechanisms of Physiopathology

Abstract

Endometriosis is a common chronic gynaecological disease causing various symptoms, such as infertility and chronic pain. The gold standard for its diagnosis is still laparoscopy and the biopsy of endometriotic lesions. Here, we aimed to compare the eutopic endometrium from women with or without endometriosis to identify proteins that may be considered as potential biomarker candidates. Eutopic endometrium was collected from patients with endometriosis (n = 4) and women without endometriosis (n = 5) during a laparoscopy surgery during the mid-secretory phase of their menstrual cycle. Total proteins from tissues were extracted and digested before LC-MS-MS analysis. Among the 5301 proteins identified, 543 were differentially expressed and enriched in two specific KEGG pathways: focal adhesion and PI3K/AKT signaling. Integration of our data with a large-scale proteomics dataset allowed us to highlight 11 proteins that share the same trend of dysregulation in eutopic endometrium, regardless of the phase of the menstrual cycle. Our results constitute the first step towards the identification of potential promising endometrial diagnostic biomarkers. They provide new insights into the mechanisms underlying endometriosis and its etiology. Our results await further confirmation on a larger sample cohort.

Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis

“…Here, utilizing advanced mass spectrometry, we generated a proteomic profile of endometriosis with the identification of 8032 unique proteins, concurrently sequencing the transcriptome of the same batch of samples. In agreement with the findings of previous reports, our study confirmed previously reported transcriptomic and proteomic changes in endometriosis, such as an increase in inflammation [12,44], the immune environment [10][11][12], and the ECM [10,12,37,38,45], along with a reduction in reproduction [46][47][48][49] related to function and pathways. Endometrial tissue refluxes into the pelvic cavity, where it implants and grows, giving rise to endometriotic lesions.…”

“…Current research aims to identify biomarkers and elucidate pathogenic mechanisms [ 8 , 9 ]. Various specimens, including endometrial tissues [ 10 , 11 ], blood [ 12 ], urine [ 13 ], peritoneal fluid [ 14 ], and follicular fluid [ 15 ], have undergone diverse omics analyses, providing valuable but predominantly single-omics-focused insights. Notably, a single gene often codes for multiple protein isoforms, each potentially serving distinct biological functions and subject to regulation by various post-translational modifications (PTMs) [ 16 , 17 ].…”

Fish Hydrolysate Supplementation Prevents Stress-Induced Dysregulation of Hippocampal Proteins Relative to Mitochondrial Metabolism and the Neuronal Network in Mice

“…Approximately 200 ng of the resulting peptide mixtures were analyzed by nanoLC-MS/MS using the protocol of Méar et al [ 17 ] also detailed in the supplementary materials and methods file .…”

Molecular Mechanisms of Endometriosis Revealed Using Omics Data

“…LAMC3 plays a role in neurogenesis; mutations in LAMC3 can cause cortical malformation [ 39 , 40 ]. LAMC3 is up-regulated in the eutopic endometrium of endometriosis [ 41 ] and in menstrual mesenchymal stem cells [ 42 ]. Basigin (BSG; CD147) is required for maintaining the Drosophila visual system; abnormal BSG causes misplacement of glial cells and disruption of capitate projections between the glia and photoreceptors in Drosophila .…”