The Apoptotic, Angiogenic and Cell Proliferation Genes CD63, S100A6 e GNB2L1 are Altered in Patients with Endometriosis

Rev Bras Ginecol Obstet. 2018 Oct;40(10):606-613. doi: 10.1055/s-0038-1673364. Epub 2018 Oct 23.

Abstract

Objective: The aim of the present study was to analyze the expression of the CD63, S100A6, and GNB2L1genes, which participate in mechanisms related to the complex pathophysiology of endometriosis.

Methods: A case-control study was conducted with 40 women who were diagnosed with endometriosis, and 15 fertile and healthy women. Paired samples of eutopic endometrium and endometriotic lesions (peritoneal and ovarian endometriotic implants) were obtained from the women with endometriosis in the proliferative (n = 20) or secretory phases (n = 20) of the menstrual cycle. As controls, paired endometrial biopsy samples were collected from the healthy women in the proliferative (n = 15) and secretory (n = 15) phases of the same menstrual cycle. We analyzed the expression levels of the CD63, S100A6, and GNB2L1 genes by real-time polymerase chain reaction.

Results: An increase in CD63, S100A6, and GNB2L1 gene transcript levels was observed in the ectopic implants compared with the eutopic endometrium of the women with and without endometriosis, regardless of the phase of the menstrual cycle.

Conclusion: These findings suggest that the CD63, S100A6, and GNB2L1 genes may be involved in the pathogenesis of endometriosis, since they participate in mechanisms such as inhibition of apoptosis, angiogenesis and cell proliferation, which lead to the loss of cell homeostasis in the ectopic endometrium, thus contributing to the implantation and survival of the tissue in the extrauterine environment.

Objetivo: O objetivo do presente estudo foi analisar a expressão dos genes CD63, S100A6 e GNB2L1, que participam em mecanismos relacionados à complexa fisiopatologia da endometriose. MéTODOS: Um estudo caso-controle foi realizado com 40 mulheres diagnosticadas com endometriose e 15 mulheres férteis e saudáveis. Amostras pareadas de endométrio eutópico e de lesões endometrióticas (implantes endometrióticos peritoneais e ovarianos) foram obtidas de mulheres com endometriose nas fases proliferativa (n = 20) ou secretora (n = 20) do ciclo menstrual. Como controle, amostras pareadas de biópsia endometrial foram coletadas de mulheres saudáveis nas fases proliferativa (n = 15) e secretora (n = 15) no mesmo ciclo menstrual. Foram analisados os níveis de expressão dos genes CD63, S100A6 e GNB2L1 por reação em cadeia da polimerase em tempo real.

Resultados: Foi observado um aumento nos níveis de transcritos dos genes CD63, S100A6 e GNB2L1 em implantes ectópicos quando comparado ao endométrio eutópico de mulheres com e sem endometriose, independente da fase do ciclo menstrual. CONCLUSãO: Estes achados sugerem que os genes CD63, S100A6 e GNB2L1 podem estar envolvidos na patogênese da endometriose, pois participam de mecanismos como inibição de apoptose, angiogênese e proliferação celular, os quais levam à perda da homeostase celular no endométrio ectópico e, portanto, contribuem para o implante e a sobrevivência do tecido no ambiente extrauterino.

MeSH terms

  • Adult
  • Apoptosis / genetics*
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Cell Proliferation / genetics*
  • Endometriosis / genetics*
  • Endometriosis / pathology*
  • Female
  • Gene Expression
  • Humans
  • Neoplasm Proteins / genetics*
  • Neovascularization, Pathologic / genetics*
  • Receptors for Activated C Kinase / genetics*
  • S100 Calcium Binding Protein A6 / genetics*
  • Tetraspanin 30 / genetics*

Substances

  • CD63 protein, human
  • Cell Cycle Proteins
  • Neoplasm Proteins
  • RACK1 protein, human
  • Receptors for Activated C Kinase
  • S100 Calcium Binding Protein A6
  • Tetraspanin 30
  • S100A6 protein, human