Inhibitory effect of resveratrol on the growth and angiogenesis of human endometrial tissue in an In Vitro three-dimensional model of endometriosis

Reprod Biol. 2020 Dec;20(4):484-490. doi: 10.1016/j.repbio.2020.07.012. Epub 2020 Sep 28.

Abstract

Endometriosis is a chronic estrogen-dependent disorder and one of the most common causes of infertility in women. Resveratrol (RES) is a polyphenolic and phytoestrogenic compound with anti-oxidative, anti-inflammatory, anti-angiogenic, and anti-estrogenic properties. The aim of the present study was to investigate the effect of different concentrations of RES on human endometrial growth and angiogenesis in an in vitro three-dimensional (3D) model of endometriosis.Human endometrial tissues of endometriosis (endometriotic) and normal (endometrial) subjects (n = 9/groups) were biopsied in sterile conditions and cut into 1 × 2 mm pieces. Tissue fragments of each biopsy were given concentrations of 0 (control), 10, 50, 100 and 200 μM RES for 21 days in 3D culture condition using fibrin as an extracellular matrix. Scoring methods were used for tissue changes, including; cellular invasion, monolayer formation and angiogenesis. Nitric oxide (NO) was measured using Griess's reaction, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the apoptotic gene expression.The mean of growth scores of endometriotic and endometrial tissue showed a significant dose dependent inhibition (P < 0.05). The levels of NO also significantly decreased in different groups. Apoptotic genes (P53, Bax, Bcl2 and caspase 3) and Sirt1 showed a significant increase in various concentrations of RES in both tissues (P < 0.05).RES exert dose- and time-dependent inhibitory effects on human endometrial tissue, and its higher doses suggested it as a natural supplement to inhibit the growth and treatment of endometriosis.

Keywords: 3D Culture; Apoptosis; Endometriosis; Nitric oxide; Resveratrol.

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biopsy
  • Dose-Response Relationship, Drug
  • Endometriosis / drug therapy*
  • Endometriosis / pathology
  • Endometrium / blood supply*
  • Endometrium / drug effects
  • Endometrium / pathology*
  • Female
  • Gene Expression
  • Humans
  • Models, Biological
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Physiologic / drug effects
  • Nitric Oxide / metabolism
  • Resveratrol / administration & dosage*
  • Tissue Culture Techniques / methods*

Substances

  • Nitric Oxide
  • Resveratrol