Advertisement

Effect of 1,25(OH)2D3 on proliferation, cell cycle, and apoptosis in endometriotic stromal cells

  • Nesa Rashidi
    Affiliations
    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
    Search for articles by this author
  • Soheila Arefi
    Affiliations
    Bahman Hospital Infertility Center, Tehran, Iran

    Genetics and in Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran, Iran
    Search for articles by this author
  • Maryam Sadri
    Affiliations
    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
    Search for articles by this author
  • Ali-Akbar Delbandi
    Correspondence
    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
    Affiliations
    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
    Search for articles by this author
Published:November 17, 2022DOI:https://doi.org/10.1016/j.rbmo.2022.11.009

      Abstract

      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.

      Design

      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.

      Results

      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).

      Conclusions

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Reproductive BioMedicine Online
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • AGIC A.
        • DJALALI S.
        • DIEDRICH K.
        • HORNUNG D.
        Apoptosis in Endometriosis.
        Gynecologic and Obstetric Investigation. 2009; 68: 217-223
        • AL-HENDY A.
        • DIAMOND M.P.
        • EL-SOHEMY A.
        • HALDER S.K.
        1,25-Dihydroxyvitamin D3 Regulates Expression of Sex Steroid Receptors in Human Uterine Fibroid Cells.
        The Journal of Clinical Endocrinology & Metabolism. 2015; 100: E572-E582
        • AMERICAN SOCIETY FOR REPRODUCTIVE, M
        Revised American Society for Reproductive Medicine classification of endometriosis: 1996.
        Fertility and Sterility. 1997; 67: 817-821
        • ARABLOU T.
        • DELBANDI A.A.
        • KHODAVERDI S.
        • AREFI S.
        • KOLAHDOUZ-MOHAMMADI R.
        • HEIDARI S.
        • MOHAMMADI T.
        • ARYAEIAN N.
        Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women.
        Phytother Res. 2019; 33: 1044-1054
        • BAO A.
        • LI Y.
        • TONG Y.
        • ZHENG H.
        • WU W.
        • WEI C.
        1,25-Dihydroxyvitamin D3 and cisplatin synergistically induce apoptosis and cell cycle arrest in gastric cancer cells.
        Int J Mol Med. 2014; 33: 1177-1184
        • BERGQVIST A.
        • BRUSE C.
        • CARLBERG M.
        • CARLSTRÖM K
        Interleukin 1β, interleukin-6, and tumor necrosis factor-α in endometriotic tissue and in endometrium.
        Fertility and Sterility - FERT STERIL. 2001; 75: 489-495
        • BHOORA S.
        • PUNCHOO R.
        Policing Cancer: Vitamin D Arrests the Cell Cycle.
        International Journal of Molecular Sciences. 2020; : 21
        • BLÄUER M.
        • ROVIO P.H.
        • YLIKOMI T.
        • HEINONEN P.K
        Vitamin D inhibits myometrial and leiomyoma cell proliferation in vitro.
        Fertility and Sterility. 2009; 91: 1919-1925
        • BOUILLON R.
        • CARMELIET G.
        • VERLINDEN L.
        • VAN ETTEN E.
        • VERSTUYF A.
        • LUDERER H.F.
        • LIEBEN L.
        • MATHIEU C.
        • DEMAY M.
        Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice.
        Endocrine Reviews. 2008; 29: 726-776
        • CERMISONI G.C.
        • ALTERI A.
        • CORTI L.
        • RABELLOTTI E.
        • PAPALEO E.
        • VIGANÒ P.
        • SANCHEZ A.M
        Vitamin D and Endometrium: A Systematic Review of a Neglected Area of Research.
        International Journal of Molecular Sciences. 2018; : 19
        • CHEGINI N.
        • ROSSI M.J.
        • MASTERSON B.J.
        Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and EGF and PDGF beta-receptors in human endometrial tissue: localization and in vitro action.
        Endocrinology. 1992; 130: 2373-2385
        • CHUANG P.-C.
        • WU M.-H.
        • SHOJI Y.
        • TSAI S.-J.
        Downregulation of CD36 results in reduced phagocytic ability of peritoneal macrophages of women with endometriosis.
        The Journal of Pathology. 2009; 219: 232-241
        • CHUNG H.W.
        • WEN Y.
        • CHOI E.A.
        • HAO L.
        • MOON H.S.
        • YU H.-K.
        • POLAN M.L.
        Pleiotrophin (PTN) and midkine (MK) mRNA expression in eutopic and ectopic endometrium in advanced stage endometriosis.
        Molecular Human Reproduction. 2002; 8: 350-355
        • CROSIGNANI P.
        • OLIVE D.
        • BERGQVIST A.
        • LUCIANO A.
        Advances in the management of endometriosis: an update for clinicians.
        Human Reproduction Update. 2006; 12: 179-189
        • DA COSTA E
        • SILVA RDE C.
        • MOURA K.K.
        • RIBEIRO JUNIOR C.L.
        • GUILLO L.A.
        2016. Estrogen signaling in the proliferative endometrium: implications in endometriosis.
        Rev Assoc Med Bras. 1992; 62: 72-77
        • DELBANDI A.-A.
        • MAHMOUDI M.
        • SHERVIN A.
        • ZARNANI A.-H.
        1,25-Dihydroxy Vitamin D3 Modulates Endometriosis-Related Features of Human Endometriotic Stromal Cells.
        American Journal of Reproductive Immunology. 2016; 75: 461-473
        • DELBANDI A.-A.
        • TORAB M.
        • ABDOLLAHI E.
        • KHODAVERDI S.
        • ROKHGIREH S.
        • MORADI Z.
        • HEIDARI S.
        • MOHAMMADI T.
        Vitamin D deficiency as a risk factor for endometriosis in Iranian women.
        Journal of Reproductive Immunology. 2021; 143103266
        • DELBANDI A.A.
        • MAHMOUDI M.
        • SHERVIN A.
        • AKBARI E.
        • JEDDI-TEHRANI M.
        • SANKIAN M.
        • KAZEMNEJAD S.
        • ZARNANI A.H.
        Eutopic and ectopic stromal cells from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.
        Fertil Steril. 2013; 100: 761-769
        • DRAETTA G.F.
        Mammalian G1 cyclins.
        Current Opinion in Cell Biology. 1994; 6: 842-846
        • FERRERO S.
        • EVANGELISTI G.
        • BARRA F.
        Current and emerging treatment options for endometriosis.
        Expert Opinion on Pharmacotherapy. 2018; 19: 1109-1125
        • GHARBARAN R.
        • ZHANG B.
        • VALERIO L.
        • ONWUMERE O.
        • WONG M.
        • MIGHTY J.
        • REDENTI S.
        Effects of vitamin D3 and its chemical analogs on the growth of Hodgkin's lymphoma, in vitro.
        BMC Research Notes. 2019; 12: 216
        • GIUDICE L.C.
        • KAO L.C.
        Endometriosis.
        The Lancet. 2004; 364: 1789-1799
        • GONZÁLEZ-PARDO V.
        • SUARES A.
        • VERSTUYF A.
        • DE CLERCQ P.
        • BOLAND R
        • BOLAND A.R.D
        Cell cycle arrest and apoptosis induced by 1α,25(OH)2D3 and TX 527 in Kaposi sarcoma is VDR dependent.
        The Journal of Steroid Biochemistry and Molecular Biology. 2014; 144: 197-200
        • GRZESIAK M.
        Vitamin D3 action within the ovary - an updated review.
        Physiological research. 2020; 69: 371-378
        • GUO S.-W.
        Recurrence of endometriosis and its control.
        Human Reproduction Update. 2009; 15: 441-461
        • HALDER S.K.
        • OSTEEN K.G.
        • AL-HENDY A.
        Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells.
        Human Reproduction. 2013; 28: 2407-2416
        • HAN J.
        • TANG Y.
        • ZHONG M.
        • WU W.
        Antitumor effects and mechanisms of 1,25(OH)2D3 in the Pfeiffer diffuse large B lymphoma cell line.
        Mol Med Rep. 2019; 20: 5064-5074
        • HARADA T.
        • KAPONIS A.
        • IWABE T.
        • TANIGUCHI F.
        • MAKRYDIMAS G.
        • SOFIKITIS N.
        • PASCHOPOULOS M.
        • PARASKEVAIDIS E.
        • TERAKAWA N.
        Apoptosis in human endometrium and endometriosis.
        Human Reproduction Update. 2004; 10: 29-38
        • HICKISH T.
        • CUNNINGHAM D.
        • COLSTON K.
        • MILLAR B.C.
        • SANDLE J.
        • MACKAY A.G.
        • SOUKOP M.
        • SLOANE J.
        The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma.
        British journal of cancer. 1993; 68: 668-672
        • HIRAKAWA T.
        • NASU K.
        • ABE W.
        • AOYAGI Y.
        • OKAMOTO M.
        • KAI K.
        • TAKEBAYASHI K.
        • NARAHARA H.
        miR-503, a microRNA epigenetically repressed in endometriosis, induces apoptosis and cell-cycle arrest and inhibits cell proliferation, angiogenesis, and contractility of human ovarian endometriotic stromal cells.
        Human Reproduction. 2016; 31: 2587-2597
        • HOLICK M.F.
        Vitamin D: A millenium perspective.
        Journal of Cellular Biochemistry. 2003; 88: 296-307
        • JIANG Q.-Y.
        • WU R.-J.
        Growth mechanisms of endometriotic cells in implanted places: a review.
        Gynecological Endocrinology. 2012; 28: 562-567
        • JONES R.K.
        • SEARLE R.F.
        • BULMER J.N.
        Apoptosis and bcl-2 expression in normal human endometrium, endometriosis and adenomyosis.
        Human Reproduction. 1998; 13: 3496-3502
        • KEANE K.N.
        • CRUZAT V.F.
        • CALTON E.K.
        • HART P.H.
        • SOARES M.J.
        • NEWSHOLME P.
        • YOVICH J.L.
        Molecular actions of vitamin D in reproductive cell biology.
        Reproduction. 2017; 153: R29-R42
        • KLEMMT P.A.B.
        • CARVER J.G.
        • KONINCKX P.
        • MCVEIGH E.J.
        • MARDON H.J.
        Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression.
        Human Reproduction. 2007; 22: 3139-3147
        • KRISHNAN A.V.
        • SWAMI S.
        • FELDMAN D.
        The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer.
        Steroids. 2012; 77: 1107-1112
        • LANGE T.S.
        • SINGH R.K.
        • KIM K.K.
        • ZOU Y.
        • KALKUNTE S.S.
        • SHOLLER G.L.
        • SWAMY N.
        • BRARD L.
        Anti-proliferative and Pro-apoptotic Properties of 3-Bromoacetoxy Calcidiol in High-risk Neuroblastoma.
        Chemical Biology & Drug Design. 2007; 70: 302-310
        • LERCHBAUM E.
        • OBERMAYER-PIETSCH B.
        Mechanisms in endocrinology - Vitamin D and fertility: A systematic review.
        European journal of endocrinology /European Federation of Endocrine Societies. 2012; 166: 765-778
        • LIU W.
        • ZHANG L.
        • XU H.-J.
        • LI Y.
        • HU C.-M.
        • YANG J.-Y.
        • SUN M.-Y.
        The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis.
        International Journal of Molecular Sciences. 2018; : 19
        • MAHONEN A.
        • PIRSKANEN A.
        • MÄENPÄÄ P.H
        Homologous and heterologous regulation of 1,25-dihydroxyvitamin D-3 receptor mRNA levels in human osteosarcoma cells.
        Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1991; 1088: 111-118
        • MAYBIN J.A.
        • CRITCHLEY H.O.D.
        Steroid regulation of menstrual bleeding and endometrial repair.
        Reviews in Endocrine and Metabolic Disorders. 2012; 13: 253-263
        • MERESMAN G.
        • VIGHI S.
        • BUQUET R.
        • CONTRERAS-ORTIZ O.
        • TESONE M.
        • RUMI L.A.
        Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis.
        Fertility and Sterility. 2000; 74: 760-766
        • MILDE-LANGOSCH K.
        • BAMBERGER A.-M.
        • GOEMANN C.
        • RÖSSING E.
        • RIECK G.
        • KELP B.
        • LÖNING T
        Expression of cell-cycle regulatory proteins in endometrial carcinomas: correlations with hormone receptor status and clinicopathologic parameters.
        Journal of Cancer Research and Clinical Oncology. 2001; 127: 537-544
        • MIYASHITA M.
        • KOGA K.
        • IZUMI G.
        • SUE F.
        • MAKABE T.
        • TAGUCHI A.
        • NAGAI M.
        • URATA Y.
        • TAKAMURA M.
        • HARADA M.
        • HIRATA T.
        • HIROTA Y.
        • WADA-HIRAIKE O.
        • FUJII T.
        • OSUGA Y.
        Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis.
        The Journal of Clinical Endocrinology & Metabolism. 2016; 101: 2371-2379
        • NARVAEZ C.J.
        • WELSH J.
        Differential Effects of 1,25-Dihydroxyvitamin D3 and Tetradecanoylphorbol Acetate on Cell Cycle and Apoptosis of MCF-7 Cells and a Vitamin D3-Resistant Variant*.
        Endocrinology. 1997; 138: 4690-4698
        • NISHIDA M.
        • NASU K.
        • UEDA T.
        • FUKUDA J.
        • TAKAI N.
        • MIYAKAWA I.
        Endometriotic cells are resistant to interferon-γ-induced cell growth inhibition and apoptosis: a possible mechanism involved in the pathogenesis of endometriosis.
        Molecular Human Reproduction. 2005; 11: 29-34
        • OLIVARES C.
        • BILOTAS M.
        • BUQUET R.
        • BORGHI M.
        • SUELDO C.
        • TESONE M.
        • MERESMAN G.
        Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis.
        Human Reproduction. 2008; 23: 2701-2708
        • PELLEGRINI C.
        • GORI I.
        • ACHTARI C.
        • HORNUNG D.
        • CHARDONNENS E.
        • WUNDER D.
        • FICHE M.
        • CANNY G.O.
        The expression of estrogen receptors as well as GREB1, c-MYC, and cyclin D1, estrogen-regulated genes implicated in proliferation, is increased in peritoneal endometriosis.
        Fertility and Sterility. 2012; 98: 1200-1208
        • PLANAS-SILVA M.D.
        • WEINBERG R.A.
        Estrogen-dependent cyclin E-cdk2 activation through p21 redistribution.
        Molecular and cellular biology. 1997; 17: 4059-4069
        • POURSOLTANI F.
        • NEJATI V.
        • PAZHANG Y.
        • REZAIE J.
        Sulindac and Vitamin D3 synergically inhibit proliferation of MCF-7 breast cancer cell through AMPK/Akt /β-catenin Axis in vitro.
        Cell Biochemistry and Function. 2021;
        • PRESS M.F.
        • XU S.H.
        • WANG J.D.
        • GREENE G.L.
        Subcellular distribution of estrogen receptor and progesterone receptor with and without specific ligand.
        The American journal of pathology. 1989; 135: 857-864
        • SERGEEV I.
        Vitamin D-mediated apoptosis in cancer and obesity.
        Hormone molecular biology and clinical investigation. 2014; 20: 43-49
        • SHARAN C.
        • HALDER S.K.
        • THOTA C.
        • JALEEL T.
        • NAIR S.
        • AL-HENDY A.
        Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase.
        Fertility and Sterility. 2011; 95: 247-253
        • SHARPE-TIMMS K.L.
        Endometrial Anomalies in Women with Endometriosis.
        Annals of the New York Academy of Sciences. 2001; 943: 131-147
        • SHIOZAWA T.
        • MIYAMOTO T.
        • KASHIMA H.
        • NAKAYAMA K.
        • NIKAIDO T.
        • KONISHI I.
        Estrogen-induced proliferation of normal endometrial glandular cells is initiated by transcriptional activation of cyclin D1 via binding of c-Jun to an AP-1 sequence.
        Oncogene. 2004; 23: 8603-8610
        • SHIOZAWA T.
        • NIKAIDO T.
        • NAKAYAMA K.
        • LU X.
        • FUJII S.
        Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of endometrium in the secretory phase and of hyperplastic endometrium treated with progesterone.
        Molecular Human Reproduction. 1998; 4: 899-905
        • SONG R.X.D.
        • SANTEN R.J.
        Membrane Initiated Estrogen Signaling in Breast Cancer1.
        Biology of Reproduction. 2006; 75: 9-16
        • TANG L.
        • WANG T.-T.
        • WU Y.-T.
        • ZHOU C.-Y.
        • HUANG H.-F.
        High expression levels of cyclin B1 and Polo-like kinase 1 in ectopic endometrial cells associated with abnormal cell cycle regulation of endometriosis.
        Fertility and Sterility. 2009; 91: 979-987
        • TANIGUCHI F.
        • KAPONIS A.
        • IZAWA M.
        • KIYAMA T.
        • DEURA I.
        • ITO M.
        • IWABE T.
        • ADONAKIS G.
        • TERAKAWA N.
        • HARADA T.
        Apoptosis and endometriosis.
        Frontiers in bioscience (Elite edition). 2011; ([Online], 3. Available) ([Accessed 2011/01//])https://doi.org/10.2741/e277
        • TAYLOR H.S.
        • KOTLYAR A.M.
        • FLORES V.A.
        Endometriosis is a chronic systemic disease: clinical challenges and novel innovations.
        The Lancet. 2021; 397: 839-852
        • VELARDE M.C.
        • AGHAJANOVA L.
        • NEZHAT C.R.
        • GIUDICE L.C.
        Increased Mitogen-Activated Protein Kinase Kinase/Extracellularly Regulated Kinase Activity in Human Endometrial Stromal Fibroblasts of Women with Endometriosis Reduces 3′,5′-Cyclic Adenosine 5′-Monophosphate Inhibition of Cyclin D1.
        Endocrinology. 2009; 150: 4701-4712
        • VERCELLINI P.
        • VIGANÒ P.
        • SOMIGLIANA E.
        • FEDELE L
        Endometriosis: pathogenesis and treatment.
        Nature Reviews Endocrinology. 2014; 10: 261-275
        • WILLIAMS G.H.
        • STOEBER K.
        The cell cycle and cancer.
        The Journal of Pathology. 2012; 226: 352-364
        • YOSHIDA S.
        • HARADA T.
        • MITSUNARI M.
        • IWABE T.
        • SAKAMOTO Y.
        • TSUKIHARA S.
        • IBA Y.
        • HORIE S.
        • TERAKAWA N.
        Hepatocyte Growth Factor/Met System Promotes Endometrial and Endometriotic Stromal Cell Invasion via Autocrine and Paracrine Pathways.
        The Journal of Clinical Endocrinology & Metabolism. 2004; 89: 823-832
        • YOTOVA I.Y.
        • QUAN P.
        • LEDITZNIG N.
        • BEER U.
        • WENZL R.
        • TSCHUGGUEL W.
        Abnormal activation of Ras/Raf/MAPK and RhoA/ROCKII signalling pathways in eutopic endometrial stromal cells of patients with endometriosis.
        Human Reproduction. 2011; 26: 885-897
        • YUGUCHI H.
        • TANABE A.
        • HAYASHI A.
        • TANAKA Y.
        • OKUDA K.
        • YAMASHITA Y.
        • TERAI Y.
        • OHMICHI M.
        The Expression Status of G Protein-Coupled Receptor GPR30 Is Associated with the Clinical Characteristics of Endometriosis.
        Endocrine Research. 2013; 38: 223-231
        • ZHANG H.
        • ZHAO X.
        • LIU S.
        • LI J.
        • WEN Z.
        • LI M.
        17βE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFκB-dependent pathway.
        Molecular and Cellular Endocrinology. 2010; 317: 31-43