Article| Volume 46, ISSUE 3, P436-445, March 2023

Effect of active vitamin D on proliferation, cell cycle and apoptosis in endometriotic stromal cells

  • Nesa Rashidi
    Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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  • Soheila Arefi
    Bahman Hospital Infertility Center, Tehran, Iran

    Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran, Iran
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  • Maryam Sadri
    Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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  • Ali-Akbar Delbandi
    Corresponding author. A-A Delbandi.
    Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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Published:November 17, 2022DOI:


      Research question

      What is the effect of vitamin D3 (1,25(OH)2D3) on proliferation, cell cycle and apoptosis of endometrial stromal cells (ESC) in endometriotic patients?


      ESC isolated from 10 women with endometriosis and 10 healthy controls were treated with 1,25(OH)2D3. The proliferation of control endometrial stromal cells (CESC), eutopic endometrial stromal cells (EuESC) and ectopic endometrial stromal cells (EESC) was analysed 72 h after the treatment using methyl thiazolyl tetrazolium assay. Propidium iodide staining and flow cytometry were used to determine the cell cycle distribution in ESC. Annexin V/propidium iodide double staining was used to evaluate apoptosis in ESC.


      In the presence of oestrogen, 1,25(OH)2D3 treatment inhibited the proliferation of ESC from all three origins (P = 0.009 for CESC, P = 0.005 for EuESC and P < 0.001 for EESC). The percentage of S phase cells in EESC was higher than in EuESC and CESC (P = 0.002 and P = 0.001, respectively). The percentage of S phase cells in EuESC was higher than in CESC (P = 0.005). The percentage of G1 phase cells in EESC was lower than that of EuESC and CESC (P = 0.003 and P = 0.002, respectively) and the percentage of G1 phase cells in EuESC was lower than that of CESC (P = 0.007). Moreover, 1,25(OH)2D3 inhibited cell cycle regardless of cell type (P = 0.002 in EESC, P = 0.001 in EuESC and P = 0.014 in CESC), but in the absence of oestrogen, inhibited cell cycle only in EuESC (P = 0.012).


      Although 1,25(OH)2D3 increased apoptotic and necrotic cells and decreased live cells in the EuESC and EESC, it did not affect apoptosis in CESC and only increased necrotic cells. These findings indicate that 1,25(OH)2D3 potentially has a growth-inhibiting and pro-apoptotic effect on ESC from endometriotic patients.


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      Ali-Akbar Delbandi was born in Tehran in 1974 and graduated in immunology at Mashhad University of Medical Sciences. He has been a faculty member at the Iran University of Medical Sciences since 2014. His research focuses on reproductive immunology with an emphasis on endometriosis.
      Key message
      The effects of 1,25(OH)2D3 (active vitamin D) on endometriosis were assessed; it prevented the proliferation of endometriotic stromal cells, and simultaneously induced apoptosis. Increased sensitivity of endometriotic cells to apoptosis might prevent the distribution and implantation of endometriotic stromal cells to ectopic sites. Vitamin D might prevent the progression of endometriosis by reducing the proliferation of these cells.