Trends in Immunotherapy

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Expressions of miR-199a-5p and miR-125b-5p and their target genes in the endometrium of recurrent implantation failure patients following in uterus infusion of autologous peripheral blood mononuclear cells

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https://doi.org/10.24294/ti.v6.i2.1457
Azarpoor, A., Ardeshirylajimi, A., Mohammadi Yeganeh, S., Pourmatrood, E., Dehghan, Z., Farifteh Nobijari, F., & Salehi, M. (2022). Expressions of miR-199a-5p and miR-125b-5p and their target genes in the endometrium of recurrent implantation failure patients following in uterus infusion of autologous peripheral blood mononuclear cells. Trends in Immunotherapy, 6(2). https://doi.org/10.24294/ti.v6.i2.1457
Volume 6 Issue 2 (2022)

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Authors

  • Azita Azarpoor
    Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences
  • Abdolreza Ardeshirylajimi Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Samira Mohammadi Yeganeh Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Elham Pourmatrood PyamIVF Co., Tehran, Iran
  • Zeinab Dehghan Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
  • Fattaneh Farifteh Nobijari Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Mohammad Salehi Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Despite numerous advances in fertility techniques, some individuals experience implantation failure. One of the therapeutic approaches is the study of immunological aspects of the implantation process in recurrent implantation failure (RIF) patients. Peripheral blood mononuclear cell (PBMC) therapy and platelet-rich plasma are currently available cell therapies. The aim of this study was to determine the expressions of the FGFR-2 and LIF genes that are regulated by miR-199a-5p and miR-125b-5p. These genes play a fundamental role in implantation in RIF patients treated with PBMCs. 20 patients clinically diagnosed with RIF were randomly assigned to a RIF patient with PBMCs intrauterine infusion group (n = 10) and RIF group (n = 10). Normal, healthy females (n = 10) comprised the control group. In order to examine the efficacy of the PBMCs injection in the treatment group, expressions of miR-199a-5p and miR-125-5p and FGFR-2 and LIF as their target genes, were evaluated in all three groups and were compared the results. We discovered that the RIF group had higher expressions of miR-199a-5p and miR-125-5p along with decreased expressions of their target genes. However, both FGFR-2 and LIF gene had elevated expressions in the RIF patients with PBMCs intrauterine infusion group compared to the RIF group, with significant decrease in miR-199a-5p and miR-125b-5p reciprocally. The treatment with PBMCs can be effective in changing the expression of microRNAs and genes associated with endometrial receptivity and by changes in the expression of them and their role during embryo development improve this process.

Keywords:

Endometrium Peripheral blood mononuclear cells repeated implantation failure microRNA

References

  1. Cakmak H, Taylor HS. Implantation failure: Molecular mechanisms and clinical treatment. Human Reproduction Update 2010; 17(2): 242–253. doi: 10.1093/humupd/dmq037.
  2. Yu N, Yang J, Guo Y, et al. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity in mice with embryonic implantation dysfunction. American Journal of Reproductive Immunology 2014; 71(1): 24–33. doi: 10.1111/aji.12150.
  3. Timeva T, Shterev A, Kyurkchiev S. Recurrent implantation failure: The role of the endometrium. Journal of Reproduction & Infertility 2014; 15(4): 173–184.
  4. Yakin K, Oktem O, Urman B. Intrauterine administration of peripheral mononuclear cells in recurrent implantation failure: A systematic review and meta-analysis. Scientific Reports 2019; 9(1): 3897.
  5. Azarpoor A, Ardeshirylajimi A, Mohammadi Yeganeh S, et al. The expression of miR-31 and its target gene FOXP3 in recurrent implantation failure patients. International Journal of Women’s Health and Reproduction Sciences 2020; 8(4): 389–395. doi: 10.15296/ijwhr.2020.62.
  6. Zadehmodarres S, Salehpour S, Saharkhiz N, et al. Treatment of thin endometrium with autologous platelet-rich plasma: A pilot study. JBRA Assisted Reproduction 2017; 21(1): 54. doi: 10.5935/1518-0557.20170013.
  7. Okitsu O, Kiyokawaa M, Oda T, et al. Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. Journal of Reproductive Immunology 2011; 92(1–2): 82–87. doi: 10.1016/j.jri.2011.07.001.
  8. Madkour A, Bouamoud N, Louanjli N, et al. Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures. Zygote 2016; 24(1): 58–69. doi: 10.1017/S0967199414000719.
  9. Rabiee S, Zamani A, Ebrahimi M, et al. Relationship of some endometrial cytokines (IL-1β, TNF-α, IP-10, MCP) with in vitro fertilization outcome. Avicenna Journal of Clinical Medicine 2015; 22(2): 99–107.
  10. Rezaee D, Bandehpour M, Kazemi B, et al. Effects of human chorionic gonadotropin-producing peripheral blood mononuclear cells on the endometrial receptivity and implantation sites of the mouse uterus. Korean Journal of Fertility and Sterility 2022; 49(4): 248–258. doi: 10.5653/cerm.2022.05358.
  11. Fujita K, Nakayama T, Takabatake K, et al. Administration of thymocytes derived from non-pregnant mice induces an endometrial receptive stage and leukaemia inhibitory factor expression in the uterus. Human Reproduction 1998; 13(10): 2888–2894. doi: 10.1093/humrep/13.10.2888.
  12. Eftekhar M, Tabibnejad N, Tabatabaie AA. The thin endometrium in assisted reproductive technology: An ongoing challenge. Middle East Fertility Society Journal 2018; 23(1): 1–7. doi: 10.1016/j.mefs.2017.12.006.
  13. Altmäe S, Martinez-Conejero JA, Esteban FJ, et al. MicroRNAs miR-30b, miR-30d, and miR-494 regulate human endometrial receptivity. Reproductive Sciences 2013; 20(3): 308–317. doi: 10.1177/1933719112453507.
  14. Hashii K, Fujiwara H, Yoshioka S, et al. Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: Possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation. Human Reproduction 1998; 13(10): 2738–2744. doi: 10.1093/humrep/13.10.2738.
  15. Salamonsen LA. Tissue injury and repair in the female human reproductive tract. Reproduction 2003; 125(3): 301–311. doi: 10.1530/rep.0.1250301.
  16. Yoshioka S, Fujiwara H, Nakayama T, et al. Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF–embryo transfer. Human Reproduction 2006; 21(12): 3290–3294. doi: 10.1093/humrep/del312.
  17. Liu W, Niu Z, Li Q, et al. MicroRNA and embryo implantation. American Journal of Reproductive Immunology 2016; 75(3): 263–271.doi: 10.1111/aji.124700.
  18. Liang J, Wang S, Wang Z. Role of microRNAs in embryo implantation. Reproductive Biology and Endocrinology 2017; 15(1): 90. doi: 10.1186/s12958-017-0309-7.
  19. Shi C, Shen H, Fan LJ, et al. Endometrial microRNA signature during the window of implantation changed in patients with repeated implantation failure. Chinese Medical Journal 2017; 130(5): 566–573. doi: 10.4103/0366-6999.20055.
  20. Chen C, Zhao Y, Yu Y, et al. MiR-125b regulates endometrial receptivity by targeting MMP26 in women undergoing IVF-ET with elevated progesterone on HCG priming day. Scientific Reports 2016; 6(1): 25302. doi: 10.1038/srep25302.
  21. Tonou-Fujimori N, Takahashi M, Onodera H, et al. Expression of the FGF receptor 2 gene (fgfr2) during embryogenesis in the zebrafish Danio rerio. Mechanisms of Development 2002; 119: S173–S178. doi: 10.1016/s0925-4773(03)00112-6.
  22. Sun YM, Lin KY, Chen YQ. Diverse functions of miR-125 family in different cell contexts. Journal of Hematology & Oncology 2013; 6(1): 6. doi: 10.1186/1756-8722-6-6.
  23. Virant-Klun I, Ståhlberg A, Kubista M, et al. MicroRNAs: From female fertility, germ cells, and stem cells to cancer in humans. Stem Cells International 2016; 2016: 3984937. doi: 10.1155/2016/3984937.
  24. Hosokawa K, Muranski P, Feng X, et al. Identification of novel microRNA signatures linked to acquired aplastic anemia. Haematologica 2015; 100(12): 1534–1545. doi: 10.3324/haematol.2015.126128.
  25. Liu T, Chen Q, Huang Y, et al. Low microRNA-199a expression in human amniotic epithelial cell feeder layers maintains human-induced pluripotent stem cell pluripotency via increased leukemia inhibitory factor expression. Acta Biochimica et Biophysica Sinica 2012; 44(3): 197–206. doi: 10.1093/abbs/gmr127.
  26. Bashiri A, Halper KI, Orvieto R. Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions. Reproductive Biology and Endocrinology 2018; 16(1): 121. doi: 10.1186/s12958-018-0414-2.
  27. Schwartz AS, Yu K, Gardenour KR, et al. Cost-effective strategies for completing the interactome. Nature Methods 2009; 6(1): 55–61. doi: 10.1038/nmeth.1283.
  28. Dehghan Z, Mirmotalebisohi SA, Sameni M, et al. A motif-based network analysis of regulatory patterns in Doxorubicin effects on treating breast cancer, a systems biology study. Avicenna Journal of Medical Biotechnology 2022; 14(2): 137–153. doi: 10.18502/ajmb.v14i2.8889.
  29. Dehghan Z, Mohammadi-Yeganeh S, Sameni M, et al. Repurposing new drug candidates and identifying crucial molecules underlying PCOS Pathogenesis Based On Bioinformatics Analysis. DARU Journal of Pharmaceutical Sciences 2021; 29(2): 353–366. doi: 10.1007/s40199-021-00413-9.
  30. Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Research 2019; 47(D1): D607–D613. doi: 10.1093/nar/gky1131.
  31. Bindea G, Mlecnik B, Hackl H, et al. ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 2009; 25(8): 1091–1093. doi: 10.1093/bioinformatics/btp101.
  32. Nobijari FF, Arefi SS, Moini A, et al. Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure. Zygote 2019; 27(4): 214–218. doi: 10.1017/S0967199419000145.
  33. Schjenken, JE, Tolosa JM, Paul JW, et al. Mechanisms of maternal immune tolerance during pregnancy. In: Zheng J (editor). Recent Advances in Research on the Human Placenta. Rijeka: InTech; 2012. p. 211–242.
  34. Kliman HJ, Frankfurter D. Clinical approach to recurrent implantation failure: Evidence-based evaluation of the endometrium. Fertility and Sterility 2019; 111(4): 618–628. doi: 10.1016/j.fertnstert.2019.02.011.
  35. Xu N, Brodin P, Wei T, et al. MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. Journal of Investigative Dermatology 2011; 131: 1521–1529. doi: 10.1038/jid.2011.55.
  36. Rouas R, Fayyad-Kazan H, El Zein N, et al. Human natural Treg microRNA signature: Role of microRNA-31 and microRNA-21 in FOXP3 expression. European Journal of Immunology 2009; 39(6): 1608–1618. doi: 10.1002/eji.200838509.
  37. Choi Y, Kim HR, Lim EJ, et al. Integrative analyses of uterine transcriptome and microRNAome reveal compromised LIF-STAT3 signaling and progesterone response in the endometrium of patients with recurrent/repeated implantation failure (RIF). PloS ONE 2016; 11(6): e0157696. doi: 10.1371/journal.pone.0157696.
  38. Yu N, Yan W, Yin T, et al. HCG-activated human peripheral blood mononuclear cells (PBMC) promote trophoblast cell invasion. PloS ONE 2015; 10(6): e0125589. doi: 10.1371/journal.pone.0125589.
  39. Galliano D, Pellicer A. MicroRNA and implantation. Fertility and Sterility 2014; 101(6): 1531–1544. doi: 10.1016/j.fertnstert.2014.04.023.
  40. Hu SJ, Ren G, Liu JL, et al. MicroRNA expression and regulation in mouse uterus during embryo implantation. Journal of Biological Chemistry 2008; 283(34): 23473–23484. doi: 10.1074/jbc.M800406200.
  41. Özcan S. MiR-30 family and EMT in human fetal pancreatic islets. Islets 2009; 1(3): 283–285. doi: 10.4161/isl.1.3.9968.
  42. Song PP, Hu Y, Liu CM, et al. Embryonic ectoderm development protein is regulated by microRNAs in human neural tube defects. American Journal of Obstetrics and Gynecology 2011; 204(6): 544.e9–544.e17. doi: 10.1016/j.ajog.2011.01.045.
  43. Li J, Donath S, Li Y, et al. miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genet 2010; 6(1): e1000795. doi: 10.1371/journal.pgen.1000795.
  44. Kresowik JD, Devor EJ, Van Voorhis BJ, et al. MicroRNA-31 is significantly elevated in both human endometrium and serum during the window of implantation: A potential biomarker for optimum receptivity. Biology of Reproduction 2014; 91(1): 17, 1–6. doi: 10.1095/biolreprod.113.116590.
  45. Tochigi H, Kajihara T, Mizuno Y, et al. Loss of miR-542-3p enhances IGFBP-1 expression in decidualizing human endometrial stromal cells. Scientific Reports 2017; 7: 40001. doi: 10.1038/srep40001.
  46. Labarta E, Martínez-Conejero JA, Alamá P, et al. Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: A functional genomics analysis. Human Reproduction 2011; 26(7): 1813–1825. doi: 10.1093/humrep/der126.