Heparin prevents oxidative stress-induced apoptosis in human decidualized endometrial stromal cells

Med Mol Morphol. 2019 Dec;52(4):209-216. doi: 10.1007/s00795-019-00220-x. Epub 2019 Mar 16.


Clinical trials have shown that administering heparin during the luteal phase has beneficial effects on implantation and live birth rates. Heparin exerts direct effects on decidual human endometrial stromal cells (HESCs), which are independent of its anticoagulant effect. However, the accurate effects of heparin on the decidualization process remain unidentified. Here, we demonstrate that HESCs become dramatically resistant to oxidative stress upon decidualization, and we hypothesize a possible direct action of heparin on the decidualization of HESCs, which would lead to improved implantation. To test this hypothesis, we established primary HESC cultures and propagated them, and then we decidualized confluent cultures with 8-bromo-cAMP, with medroxyprogesterone acetate, and with or without heparin. We treated the cells with hydrogen peroxide (H2O2) as a source of reactive oxygen species (ROS). Adding heparin to decidualized HESCs induced prolactin secretion. Decidualized HESCs treated with heparin were prevented from undergoing apoptosis induced by oxidative stress. Heparin induced nuclear accumulation of the forkhead transcription factor FOXO1 and expression of its downstream target, the ROS scavenger superoxide dismutase 2. These results demonstrate that heparin-treated decidualized HESCs acquired further resistance to oxidative stress, suggesting that heparin may improve the implantation environment.

Keywords: Endometrial decidualization; FOXO1; Heparin; Oxidative stress; SOD2.

MeSH terms

  • Apoptosis / drug effects*
  • Cells, Cultured
  • Decidua / metabolism*
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Forkhead Box Protein O1 / metabolism
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation / drug effects
  • Heparin / pharmacology*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Oxidative Stress / drug effects*
  • Progesterone / metabolism
  • Reactive Oxygen Species / metabolism
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism
  • Superoxide Dismutase / metabolism


  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Reactive Oxygen Species
  • Progesterone
  • Heparin
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • superoxide dismutase 2