Molecular signature of eutopic endometrium in endometriosis based on the multi-omics integrative synthesis.

To synthesise data from genome-wide studies reporting molecular signature of eutopic endometrium through the phases of the menstrual cycle in endometriosis. Extraction of data from publications reporting genetic signatures characterising endometrium associated with endometriosis. The nomenclature of extracted differentially expressed transcripts and proteins was adopted according to the HUGO Gene Nomenclature Committee (HGNC). Loci were further sorted according to the different phases of the menstrual cycle, i.e. menstrual (M), proliferative (P), secretory (S), early-secretory (ES), mid-secretory (MS), late-secretory (LS), and not specified (N/S) if the endometrial dating was not available. Enrichment analysis was performed using the DAVID bioinformatics tool. Altered molecular changes were reported by 21 studies, including 13 performed at the transcriptomic, 6 at proteomic, and 2 at epigenomic level. Extracted data resulted in a catalogue of total 670 genetic causes with available 591 official gene symbols, i.e. M = 3, P = 188, S = 81, ES = 82, MS = 173, LS = 36, and N/S = 28. Enriched pathways included oestrogen signalling pathway, extracellular matrix organization, and endothelial cell chemotaxis. Our study revealed that knowledge of endometrium biology in endometriosis is fragmented due to heterogeneity of published data. However, 15 genes reported as dysregulated by at least two studies within the same phase and 33 significantly enriched GO-BP terms/KEGG pathways associated with different phases of the menstrual cycle were identified. A multi-omics insight into molecular patterns underlying endometriosis could contribute towards identification of endometrial pathological mechanisms that impact fertility capacities of women with endometriosis.