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.
Highlights
Embryo implantation, characterised by synchronised interaction between vital embryo and maternal receptive endometrium [1], is restricted to the short time window of implantation (WOI), which appears in the mid-secretory (MS) phase of the menstrual cycle [2]
The aims of the present study were to (1) screen for reported transcripts/proteins associated with endometrial receptivity in adenomyosis, endometriosis and healthy women; (2) edit the nomenclature of extracted transcripts/proteins to develop gene lists specific for adenomyosis, endometriosis and healthy groups; (3) obtain enriched pathways associated with retrieved genes using bioinformatics network and functional enrichment-based approaches; (4) prioritise candidate genes for validation experiment; and (5) analyse expression patterns of selected genes in endometrial biopsy samples collected during expected windows of receptivity in women with and without adenomyosis
Selected genes were analysed for expression levels in endometrial biopsy samples collected during the expected window of receptivity in women with and without adenomyosis who underwent assisted reproductive technique (ART) treatment
Summary
Embryo implantation, characterised by synchronised interaction between vital embryo and maternal receptive endometrium [1], is restricted to the short time window of implantation (WOI), which appears in the mid-secretory (MS) phase of the menstrual cycle [2]. 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. 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. 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
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