PreImplantation Factor in endometriosis: A potential role in inducing immune privilege for ectopic endometrium

PLoS One. 2017 Sep 13;12(9):e0184399. doi: 10.1371/journal.pone.0184399. eCollection 2017.

Abstract

Endometriosis is a chronic inflammatory condition characterised by the growth of endometrial epithelial and stromal cells outside the uterine cavity. In addition to Sampson's theory of retrograde menstruation, endometriosis pathogenesis is facilitated by a privileged inflammatory microenvironment, with T regulatory FoxP3+ expressing T cells (Tregs) being a significant factor. PreImplantation Factor (PIF) is a peptide essential for pregnancy recognition and development. An immune modulatory function of the synthetic PIF analog (sPIF) has been successfully confirmed in multiple animal models. We report that PIF is expressed in the epithelial ectopic cells in close proximity to FoxP3+ stromal cells. We provide evidence that PIF interacts with FoxP3+ cells and modulates cell viability, dependent on cell source and presence of inflammatory mediators. Our finding represent a novel PIF-based mechanism in endometriosis that has potential for novel therapeutics.

MeSH terms

  • Cells, Cultured
  • Choristoma / genetics
  • Choristoma / metabolism
  • Choristoma / pathology
  • Endometriosis / genetics
  • Endometriosis / immunology*
  • Endometriosis / pathology
  • Endometrium / immunology*
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / genetics*
  • Ovarian Diseases / genetics
  • Ovarian Diseases / immunology
  • Ovarian Diseases / pathology
  • Peritoneal Diseases / genetics
  • Peritoneal Diseases / immunology
  • Peritoneal Diseases / pathology
  • Pregnancy
  • Pregnancy Complications / genetics
  • Pregnancy Complications / immunology
  • Pregnancy Complications / pathology
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / metabolism
  • Pregnancy Proteins / pharmacology
  • Pregnancy Proteins / physiology*
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transcriptome / drug effects

Substances

  • Pregnancy Proteins
  • preimplantation factor, human

Grants and funding

Dr. Eytan R. Barnea is the (uncompensated) Chief Scientist for BioIncept, LLC. Martin Mueller received an unrestricted grant from BioIncept. This grant aims to prepare PIF clinical trial in the field of neonatal brain injuries. BioIncept, LLC did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of the authors is articulated in the ‘author contributions’ section.