Profiling of selected angiogenesis-related genes in proliferative eutopic endometrium of women with endometriosis

Eur J Obstet Gynecol Reprod Biol. 2014 Jan:172:85-92. doi: 10.1016/j.ejogrb.2013.10.007. Epub 2013 Oct 14.

Abstract

Objective: To compare the expression level of the most relevant angiogenesis-related genes in the eutopic endometrium of women with and without endometriosis.

Study design: 32 regularly menstruating patients (18 with endometriosis and 14 controls) underwent surgery in the proliferative phase of the cycle. Eutopic endometrium was collected by the use of aspirating biopsy prior to laparoscopy. Only patients with advanced (stage III and IV) histopathologically confirmed ovarian endometriosis were studied. Real-time PCR gene arrays were applied to examine the expression of 84 human angiogenesis-connected genes. Western-blot and enzyme-linked immunosorbent assays (ELISA) were used to confirm the expression of selected proteins.

Results: We found significantly higher levels of AKT1 (p=0.003), TYMP (p=0.02), JAG1 (p=0.007), LAMA5 (p=0.005) and TIMP-1 (p=0.03) in eutopic endometrium of patients with endometriosis as compared with controls. By the use of Western blot we found clearly positive expression of AKT1 whereas ELISA assays confirmed expression of AKT1, TYMP, JAG1, LAMA5 and TIMP1.

Conclusion: Changes in the expression of selected genes might lead to or be a consequence of an early defect in the physiological activity of proliferative endometrium ultimately resulting in its overgrowth outside the uterine cavity.

Keywords: Angiogenesis; Endometriosis; Eutopic endometrium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Case-Control Studies
  • Endometriosis / genetics*
  • Endometriosis / metabolism
  • Endometrium / blood supply
  • Endometrium / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follicular Phase / genetics*
  • Follicular Phase / metabolism
  • Gene Expression Profiling
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Jagged-1 Protein
  • Laminin / genetics
  • Laminin / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic / genetics*
  • Ovarian Diseases / genetics*
  • Ovarian Diseases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / analysis*
  • Real-Time Polymerase Chain Reaction
  • Serrate-Jagged Proteins
  • Thymidine Phosphorylase / genetics
  • Thymidine Phosphorylase / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Young Adult

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Laminin
  • Membrane Proteins
  • RNA, Messenger
  • Serrate-Jagged Proteins
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • laminin alpha5
  • TYMP protein, human
  • Thymidine Phosphorylase
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt