Determining the Molecular Background of Endometrial Receptivity in Adenomyosis

Biomolecules. 2020 Sep 11;10(9):1311. doi: 10.3390/biom10091311.

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.

Keywords: adenomyosis; candidate genes; endometrial receptivity; endometriosis; gene expression; gene set enrichment analysis (GSEA); multi-omics; protein–protein interaction network (PPIN).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomyosis / genetics*
  • Adenomyosis / metabolism
  • Adenomyosis / pathology
  • Adult
  • Case-Control Studies
  • Endometriosis / genetics*
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Humans
  • Infertility, Female / genetics*
  • Infertility, Female / metabolism
  • Infertility, Female / pathology
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism
  • Protein Interaction Mapping
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein / genetics
  • Suppressor of Cytokine Signaling 3 Protein / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • FOS protein, human
  • IL10 protein, human
  • IL13 protein, human
  • IL4 protein, human
  • IL6 protein, human
  • Interleukin-13
  • Interleukin-6
  • JunB protein, human
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Proto-Oncogene Proteins c-fos
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Transcription Factors
  • Interleukin-10
  • Interleukin-4