Determining the Molecular Background of Endometrial Receptivity in Adenomyosis

Abstract

Background: Adenomyosis is a gynaecological condition with limited evidence of negative impact to endometrial receptivity. It is commonly associated with endometriosis, which has been shown to alter endometrial expression patterns. Therefore, the candidate genes identified in endometriosis could serve as a source to study endometrial function in adenomyosis. Methods: Transcripts/proteins associated with endometrial receptivity in women with adenomyosis or endometriosis and healthy women were obtained from publications and their nomenclature was adopted according to the HUGO Gene Nomenclature Committee (HGNC). Retrieved genes were analysed for enriched pathways using Cytoscape/Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Reactome tools to prioritise candidates for endometrial receptivity. These were used for validation on women with (n = 9) and without (n = 13) adenomyosis. Results: Functional enrichment analysis of 173, 42 and 151 genes associated with endometriosis, adenomyosis and healthy women, respectively, revealed signalling by interleukins and interleukin-4 and interleukin-13 signalling pathways, from which annotated LIF, JUNB, IL6, FOS, IL10 and SOCS3 were prioritised. Selected genes showed downregulated expression levels in adenomyosis compared to the control group, but without statistical significance. Conclusion: This is the first integrative study providing putative candidate genes and pathways characterising endometrial receptivity in women with adenomyosis in comparison to healthy women and women with endometriosis.

Current and Future Roles of Circular RNAs in Normal and Pathological Endometrium

“…The ceRNA networks included 122 miRNAs and 137 mRNAs, which were closely related to nine signaling pathways. Some of them, such as Rap1 pathway ( 30 ) and leukocyte transendothelial migration pathway(including Intercellular Adhesion Molecule 1[ICAM-1) and Integrin Subunit Alpha L (ITGAL)] ( 31 , 32 ), have been proven as involved in endometriosis. The data suggest that these pathways might play a role in the pathogenesis and development of endometriosis via interacting with circRNAs.…”

Transcriptomics of receptive endometrium in women with sonographic features of adenomyosis

“…In our previous study [ 18 ], we gathered proteins, genes and functional noncoding RNAs (ncRNAs) shown to be dysregulated in the endometrium of women with adenomyosis during the expected window of implantation (WOI). Bioinformatics approaches were used to integrate retrieved loci with endometrial receptivity genes from the literature associated with healthy (normal) uteri to identify candidate dysregulated mechanisms involved in the regulation of embryo implantation in adenomyosis.…”

“…Bioinformatics approaches were used to integrate retrieved loci with endometrial receptivity genes from the literature associated with healthy (normal) uteri to identify candidate dysregulated mechanisms involved in the regulation of embryo implantation in adenomyosis. In addition, we included better characterized endometriosis as a model disorder to study the impact of gynaecological pathology on endometrial molecular organization [ 18 ]. Numerous published genome-wide studies associated with the endometrial molecular background in women with endometriosis enabled us to develop a catalogue of genes sorted according to the phases of the menstrual cycle [ 19 ].…”

“…Numerous published genome-wide studies associated with the endometrial molecular background in women with endometriosis enabled us to develop a catalogue of genes sorted according to the phases of the menstrual cycle [ 19 ]. Genes sorted in the mid-secretory phase corresponding to the appearance of the WOI were used for the integrative analysis mentioned above [ 18 ]. The identified enriched “Signalling by interleukins” and “Interleukin-4 and interleukin-13 signalling” pathways were prioritized, and the corresponding mapped LIF , SOCS3 , IL10 , IL6 , JUNB and FOS genes were validated.…”

“…The identified enriched “Signalling by interleukins” and “Interleukin-4 and interleukin-13 signalling” pathways were prioritized, and the corresponding mapped LIF , SOCS3 , IL10 , IL6 , JUNB and FOS genes were validated. Since downregulated expression levels of selected genes in adenomyosis compared to the control group showed no statistical significance, we assumed that comprehensive endometrial transcriptomics profiling would be an appropriate next step to identify adenomyosis-specific loci [ 18 ].…”