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Therapeutic effect of human umbilical cord mesenchymal stem cells on tubal factor infertility using a chronic salpingitis murine model

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Background

The study was conducted to evaluate the application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of tubal factor infertility (TFI) caused by Chlamydia trachomatis, and investigate their effect on fertility in animal models of chronic salpingitis.

Methods

In this study, we investigated the therapy effects of the transplantation of hUCMSCs in tubal factor infertility using a chronic salpingitis murine model which induced Chlamydia trachomatis. Twenty rats were divided into two groups: control group (n = 10) and treatment group (n = 10). hUCMSCs were given to mice after exposure to C. trachomatis for 4 weeks. After treatment for 4 weeks, five mice were randomly selected from each of the two groups to sacrifice and we examined the organ morphology and pathology, inflammatory cytokines, proliferation, and apoptosis in fallopian tube (FT).The remaining five mice from each group were caged 2:1 with male mice for another 4 weeks, the numbers of pregnant mice and the mean number of pups in the different groups were enumerated and calculated.

Results

Intravaginal inoculation of hUCMSCs alleviated hydrosalpinx of the oviduct. EdU-labeled hUCMSCs are located at the interstitial site of the fallopian tube. Macrophage (F4/80) infiltration was significantly reduced in the treatment group compared with the control group and expression levels of the anti-inflammatory cytokine IL10 were increased after hUCMSCs treatment. Furthermore, mRNA and protein expression levels of PCNA and Caspase-3 were increased and decreased, respectively, in the hUCMSCs’ treatment group compared with the control. Moreover, hUCMSCs’ transplantation improved murine fertility.

Conclusions

Anti-inflammatory and anti-apoptotic effects of hUCMSCs may play an important role in TFI. Our data suggest that hUCMSCs’ transplantation contributed to the repair of tubal injury and improvement of fertility, providing a basis for assessing the contribution of stem cells in the oviduct for direct repair of the tube to assist reproduction.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

hUCMSCs:

Human umbilical cord mesenchymal stem cells

MSCs:

Mesenchymal stem cells

TFI:

Tubal factor infertility

FT:

Fallopian tube

IL-10:

Interleukin-10

PCNA:

Proliferating cell nuclear antigen

Caspase-3:

Cysteine-containing aspartate-specific protease

References

  1. Detels R, Green AM, Klausner JD et al (2011) The incidence and correlates of symptomatic and asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae infections in selected populations in five countries. Sex Transm Dis 38:503–509

    PubMed  PubMed Central  Google Scholar 

  2. Ison CA (2012) Antimicrobial resistance in sexually transmitted infections in the developed world: implications for rational treatment. Curr Opin Infect Dis 25:73–78

    Article  CAS  PubMed  Google Scholar 

  3. Mirza R, DiPietro LA, Koh TJ (2009) Selective and specific macrophage ablation is detrimental to wound healing in mice. Am J Pathol 175:2454–2462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Stappenbeck TS, Miyoshi H (2009) The role of stromal stem cells in tissue regeneration and wound repair. Science 324:1666–1669

    Article  CAS  PubMed  Google Scholar 

  5. Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 127:514–525

    Article  CAS  PubMed  Google Scholar 

  6. Shi Y, Su J, Roberts AI et al (2012) How mesenchymal stem cells interact with tissue immune responses. Trends Immunol 33:136–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rastegar F, Shenaq D, Huang J et al (2010) Mesenchymal stem cells: molecular characteristics and clinical applications. World J Stem Cells 2:67–80

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nagaishi K, Arimura Y, Fujimiya M (2015) Stem cell therapy for inflammatory bowel disease. J Gastroenterol 50:280–286

    Article  CAS  PubMed  Google Scholar 

  9. Kim HS, Yun JW, Shin TH et al (2015) Human umbilical cord blood mesenchymal stem cell-derived PGE2 and TGF-beta1 alleviate atopic dermatitis by reducing mast cell degranulation. Stem Cells 33:1254–1266

    Article  CAS  PubMed  Google Scholar 

  10. Shin TH, Kim HS, Kang TW et al (2016) Human umbilical cord blood-stem cells direct macrophage polarization and block inflammasome activation to alleviate rheumatoid arthritis. Cell DEATH DIS 7:e2524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Uccelli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8:726–736

    Article  CAS  PubMed  Google Scholar 

  12. Ma S, Xie N, Li W et al (2014) Immunobiology of mesenchymal stem cells. Cell Death Differ 21:216–225

    Article  CAS  PubMed  Google Scholar 

  13. English K (2013) Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol 91:19–26

    Article  CAS  PubMed  Google Scholar 

  14. Kestendjieva S, Kyurkchiev D, Tsvetkova G et al (2008) Characterization of mesenchymal stem cells isolated from the human umbilical cord. Cell Biol Int 32:724–732

    Article  CAS  PubMed  Google Scholar 

  15. Lu LL, Liu YJ, Yang SG et al (2006) Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 91:1017–1026

    CAS  PubMed  Google Scholar 

  16. Weiss ML, Anderson C, Medicetty S et al (2008) Immune properties of human umbilical cord Wharton's jelly-derived cells. Stem Cells 26:2865–2874

    Article  CAS  PubMed  Google Scholar 

  17. Zhao J, Zhang Q, Wang Y et al (2015) Uterine infusion with bone marrow mesenchymal stem cells improves endometrium thickness in a rat model of thin endometrium. Reprod Sci 22:181–188

    Article  PubMed  PubMed Central  Google Scholar 

  18. Elfayomy AK, Almasry SM, El-Tarhouny SA et al (2016) Human umbilical cord blood-mesenchymal stem cells transplantation renovates the ovarian surface epithelium in a rat model of premature ovarian failure: possible direct and indirect effects. Tissue Cell 48:370–382

    Article  CAS  PubMed  Google Scholar 

  19. Han YF, Tao R, Sun TJ et al (2013) Optimization of human umbilical cord mesenchymal stem cell isolation and culture methods. Cytotechnology 65:819–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lin G, Huang YC, Shindel AW et al (2009) Labeling and tracking of mesenchymal stromal cells with EdU. Cytotherapy 11:864–873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hunter RH (2005) The Fallopian tubes in domestic mammals: how vital is their physiological activity? Reprod Nutr Dev 45:281–290

    Article  PubMed  Google Scholar 

  22. Cho DI, Kim MR, Jeong HY et al (2014) Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages. Exp Mol Med 46:e70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wise AF, Williams TM, Kiewiet MB et al (2014) Human mesenchymal stem cells alter macrophage phenotype and promote regeneration via homing to the kidney following ischemia-reperfusion injury. Am J Physiol Renal Physiol 306:F1222–F1235

    Article  CAS  PubMed  Google Scholar 

  24. Spaeth E, Klopp A, Dembinski J et al (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 15:730–738

    Article  CAS  PubMed  Google Scholar 

  25. Du H, Taylor HS (2010) Stem cells and reproduction. Curr Opin Obstet Gynecol 22:235–241

    Article  PubMed  PubMed Central  Google Scholar 

  26. Deng J, Petersen BE, Steindler DA et al (2006) Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24:1054–1064

    Article  CAS  PubMed  Google Scholar 

  27. Xin G, Du J, Zhang J et al (2014) Novel reversible permanent contraception: an animal experiment of embedding contraceptive surgery in the fimbriated extremity of the fallopian. J Obstet Gynaecol Res 40:1907–1912

    Article  PubMed  Google Scholar 

  28. Qin Z, Bai Z, Sun Y et al (2016) PCNA-Ub polyubiquitination inhibits cell proliferation and induces cell-cycle checkpoints. Cell Cycle 15:3390–3401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nicolay NH, Ruhle A, Perez RL et al (2016) Mesenchymal stem cells are sensitive to bleomycin treatment. Sci Rep 6:26645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Xu M, Uemura R, Dai Y et al (2007) In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function. J Mol Cell Cardiol 42:441–448

    Article  CAS  PubMed  Google Scholar 

  31. Liang W, Lu C, Li J et al (2010) p73alpha regulates the sensitivity of bone marrow mesenchymal stem cells to DNA damage agents. Toxicology 270:49–56

    Article  CAS  PubMed  Google Scholar 

  32. Li Z, Zhang Z, Chen X, et al. Treatment evaluation of Wharton’s jelly-derived mesenchymal stem cells using a chronic salpingitis model: an animal experiment. STEM CELL RES THER. 2017;8.

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Acknowledgements

The authors thank the Institute of Vaccines at the Third Affiliated Hospital of Sun Yat-sen University of the People's Republic of China for their help with study experimentation. We also thank all members in the department of Gynecology at the Third Affiliated Hospital of Sun Yat-sen University for their scientific advice and encouragement.

Funding

This study was supported by Wu Jieping Fund Medical Association (320.6755.15012) and Guangzhou Scientific Research Project (201607010085).

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Authors

Contributions

XM-L, TL, and XR-T conceived and designed the experiments. WJ-L, XM-L, TL, and XR-T performed the experiments. WJ-L and XR-T analyzed the data. WJ-L, XM-L, and TL contributed reagents/materials/analysis tools. WJ-L and XR-T wrote the paper. All authors read and approved the final manuscript. Ethics approval and consent to participate.This study was approved by the Ethics Committee of the the Third Affiliated Hospital of Sun Yat-sen University and run in accordance with the guidelines of the Helsinki Declaration. All participants provided written informed consent to participate in this study. All of the hUCMSCs in our study were manufactured and provided by the International Stem Cell Joint Research Center of Boyalife Stem Cell Technology Co., Ltd., Jiangsu province of China. All female and male C3H/HeN mice were were provided by the Beijing Vital-China Laboratory Animal Technology Co., Ltd.; (qualification no. SCXY (Beijing) 2016 - 0011). The Institute of Vaccines at the Third Affiliated Hospital of Sun Yat-sen University of the People's Republic of China approved the animal experimental protocol. Animals were used in accordance with the Animal Care and Use Committee of Sun Yat-sen University.

Corresponding author

Correspondence to Xiaomao Li.

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The authors declare no conflict of interest.

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Liao, W., Tang, X., Li, X. et al. Therapeutic effect of human umbilical cord mesenchymal stem cells on tubal factor infertility using a chronic salpingitis murine model. Arch Gynecol Obstet 300, 421–429 (2019). https://doi.org/10.1007/s00404-019-05209-6

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  • DOI: https://doi.org/10.1007/s00404-019-05209-6

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