Effect of 1,25(OH)2D3 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 Ali-Akbar Delbandi, Department of Immunology, School of Medicine; Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Theran, Iran
    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

      To evaluate Vitamin D3 (1,25(OH)2D3(effect on proliferation, cell cycle, and apoptosis of endometrial stromal cells (ESCs) in endometriotic patients.


      ESCs isolated from ten women with endometriosis and ten healthy controls were treated with 1,25(OH)2D3. The proliferation of Control Endometrial Stromal Cells (CESCs), Eutopic Endometrial Stromal Cells (EuESCs), and Ectopic Endometrial Stromal Cells (EESCs) was analyzed 72h after the treatment using MTT assay. Propidium iodide (PI) staining and flow cytometric were used to determine the cell cycle distribution in ESCs. Annexin V-PI double staining was used to evaluate apoptosis in ESCs.


      In the presence of estrogen, 1,25(OH)2D3 treatment inhibited the proliferation of ESCs from all three origins (P˂0.01 for CESCs and EuESCs and P˂0.001 for EESCs). Percentage of S phase cells in EESCs was higher than in EuESCs and CESCs (P˂0.01). Percentage of S phase cells in EuESCs was higher than in CESCs (P˂0.01). Percentage of G1 phase cells in EESCs was lower than that of EuESCs and CESCs, and the percentage of G1 phase cells in EuESCs was lower than that of CESCs (P˂0.01). Moreover, 1,25(OH)2D3 inhibited cell cycle regardless of cell type (P<0.01 in EESCs and EuESCs and P<0.05 in CESCs), but estrogen absence inhibited cell cycle only in EuESCs (P<0.05).


      Although 1,25(OH)2D3 increased apoptotic and necrotic cells and decreased living cells in the EuESCs and EESCs, it did not affect apoptosis in CESCs and only increased necrotic cells. Our findings indicate that 1,25(OH)2D3 potentially has a growth-inhibiting and pro-apoptotic effect on ESCs from endometriotic patients.


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