Clinical Science

Review article

Genetic, epigenetic and stem cell alterations in endometriosis: new insights and potential therapeutic perspectives

Amalia Forte, Marilena Cipollaro, Umberto Galderisi


Human endometrium is a highly dynamic tissue, undergoing periodic growth and regression at each menstrual cycle. Endometriosis is a frequent chronic pathological status characterized by endometrial tissue with an ectopic localization, causing pelvic pain and infertility and a variable clinical presentation. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation in approximately 1.0% of affected women, with the involvement of multiple pathways of development. Increasing evidence supports a key contribution of different stem/progenitor cell populations not only in the cyclic regeneration of eutopic endometrium, but also in the pathogenesis of at least some types of endometriosis. Evidence has arisen from experiments in animal models of disease through different kinds of assays (including clonogenicity, the label-retaining cell approach, the analysis of undifferentiation markers), as well as from descriptive studies on ectopic and eutopic tissue samples harvested from affected women. Changes in stem cell populations in endometriotic lesions are associated with genetic and epigenetic alterations, including imbalance of miRNA expression, histone and DNA modifications and chromosomal aberrations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem/progenitor cells in eutopic endometrium and the aetiology of endometriosis, together with a report of the most recently identified genetic and epigenetic alterations in endometriosis. We also describe the potential advantages of single cell molecular profiling in endometrium and in endometriotic lesions. All these data can have clinical implications and provide a basis for new potential therapeutic applications.

  • endometriosis
  • epigenetics
  • epithelial progenitor cell
  • mesenchymal stromal cell
  • microRNA
  • stem cell marker

Abbreviations: APC, adenomatous polyposis coli; CGH, comparative genomic hybridization; ChIP, chromatin immunoprecipitation; CSC, cancer stem cell; CXCR4, CXC chemokine receptor 4; EMP, endometrial main population; EPC, endothelial progenitor cell; ESP, endometrial side-population; HDAC, histone deacetylase; HLA, human leucocyte antigen; IPO13, importin13; LOC, lab-on-a-chip; LRC, label-retaining cell; MSC, mesenchymal stromal cell; NGS, next-generation sequencing; Oct, octamer-binding protein; PTEN, phosphatase and tensin homologue deleted on chromosome 10; RT, reverse transcription; SDF-1α, stromal-cell-derived factor 1α; SP, side-population; TLR, Toll-like receptor; UTR, untranslated region; VEGF-A, vascular endothelial growth factor A

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