Skip to main content

Advertisement

Log in

POSTN Promotes the Proliferation of Spermatogonial Cells by Activating the Wnt/β-Catenin Signaling Pathway

  • Male Reproduction: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The self-renewal of spermatogonial cells (SCs) provides the foundation for life-long spermatogenesis. To date, only a few growth factors have been used for the culture of SCs in vitro, and how to enhance proliferation capacity of SCs in vitro needs further research. This study aimed to explore the effects of periostin (POSTN) on the proliferation of human SCs. GC-1 spg cells were cultured in a medium with POSTN, cell proliferation was evaluated by MTS analysis and EdU assay, and the Wnt/β-catenin signaling pathway was examined. Thereafter, the proliferations of human SC were detected using immunofluorescence and RT-PCR. In this study, we found that CM secreted by human amniotic mesenchymal stem cells (hAMSCs) could enhance the proliferation capacity of mouse GC-1 spg cells. Label-free mass spectrometry and ELISA analysis demonstrated that high level of POSTN was secreted by hAMSCs. MTS and EdU staining showed that POSTN increased GC-1 spg cell proliferation, whereas CM from POSTN-silenced hAMSCs suppressed cell proliferation capacity. Then POSTN was found to activate the Wnt/β-catenin signaling pathway to regulate the proliferation of GC-1 spg cells. XAV-939, a Wnt/β-catenin inhibitor, partially reversed the effects of POSTN on GC-1 spg cell proliferation. We then analyzed human SCs and found that POSTN promoted human SC proliferation in vitro. These findings provide insights regarding the role of POSTN in regulating SC proliferation via the Wnt/β-catenin signaling pathway and suggest that POSTN may serve as a cytokine for male infertility therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

SC:

spermatogonial cell

hAMSCs:

human amniotic mesenchymal stem cells

CM:

condition medium

hAECs:

human amniotic epithelial cells

ESCs:

human embryonic stem cells

References

  1. Toolee H, Rastegar T, Solhjoo S, Mortezaee K, Mohammadipour M, Kashani IR, et al. Roles for Kisspeptin in proliferation and differentiation of spermatogonial cells isolated from mice offspring when the cells are cocultured with somatic cells. J Cell Biochem. 2019;120(4):5042–54. https://doi.org/10.1002/jcb.27780.

    Article  CAS  PubMed  Google Scholar 

  2. Sahare MG. Suyatno, Imai H. Recent advances of in vitro culture systems for spermatogonial stem cells in mammals. Reprod Med Biol. 2018;17(2):134–42. https://doi.org/10.1002/rmb2.12087.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Liu T, Guo L, Liu Z, Cheng W. Human amniotic epithelial cells maintain mouse spermatogonial stem cells in an undifferentiated state due to high leukemia inhibitor factor (LIF) expression. In Vitro Cell Dev Biol Anim. 2011;47(4):318–26. https://doi.org/10.1007/s11626-011-9396-5.

    Article  CAS  PubMed  Google Scholar 

  4. Koruji M, Shahverdi A, Janan A, Piryaei A, Lakpour MR, Gilani SM. Proliferation of small number of human spermatogonial stem cells obtained from azoospermic patients. J Assist Reprod Genet. 2012;29(9):957–67. https://doi.org/10.1007/s10815-012-9817-8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. He Y, Chen X, Zhu H, Wang D. Developments in techniques for the isolation, enrichment, main culture conditions and identification of spermatogonial stem cells. CYTOTECHNOLOGY. 2015;67(6):921–30. https://doi.org/10.1007/s10616-015-9850-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Meirelles LS, Fontes AM, Covas DT, Caplan AI. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev. 2009;20(5-6):419–27. https://doi.org/10.1016/j.cytogfr.2009.10.002.

    Article  CAS  Google Scholar 

  7. Saheli M, Bayat M, Ganji R, Hendudari F, Kheirjou R, Pakzad M, et al. Human mesenchymal stem cells-conditioned medium improves diabetic wound healing mainly through modulating fibroblast behaviors. Arch Dermatol Res. 2020;312(5):325–36. https://doi.org/10.1007/s00403-019-02016-6.

    Article  CAS  PubMed  Google Scholar 

  8. Ge L, Jiang M, Duan D, Wang Z, Qi L, Teng X, et al. Secretome of olfactory mucosa mesenchymal stem cell, a multiple potential stem cell. Stem Cells Int. 2016;2016:1243659–16. https://doi.org/10.1155/2016/1243659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pischiutta F, Brunelli L, Romele P, Silini A, Sammali E, Paracchini L, et al. Protection of brain injury by amniotic mesenchymal stromal cell-secreted metabolites. Crit Care Med. 2016;44(11):e1118–31. https://doi.org/10.1097/CCM.0000000000001864.

    Article  CAS  PubMed  Google Scholar 

  10. He D, Zhao F, Jiang H, Kang Y, Song Y, Lin X, et al. LOXL2 from human amniotic mesenchymal stem cells accelerates wound epithelialization by promoting differentiation and migration of keratinocytes. Aging (Albany NY). 2020;12(13):12960–86. https://doi.org/10.18632/aging.103384.

    Article  CAS  Google Scholar 

  11. Idolazzi L, Ridolo E, Fassio A, Gatti D, Montagni M, Caminati M, et al. Periostin: the bone and beyond. EUR J INTERN MED. 2017;38:12–6. https://doi.org/10.1016/j.ejim.2016.11.015.

    Article  CAS  PubMed  Google Scholar 

  12. Lambert AW, Wong CK, Ozturk S, Papageorgis P, Raghunathan R, Alekseyev Y, et al. Tumor cell-derived periostin regulates cytokines that maintain breast cancer stem cells. Mol Cancer Res. 2016;14(1):103–13. https://doi.org/10.1158/1541-7786.MCR-15-0079.

    Article  CAS  PubMed  Google Scholar 

  13. Kormann R, Kavvadas P, Placier S, Vandermeersch S, Dorison A, Dussaule JC, et al. Periostin promotes cell proliferation and macrophage polarization to drive repair after AKI. J Am Soc Nephrol. 2020;31(1):85–100. https://doi.org/10.1681/ASN.2019020113.

    Article  CAS  PubMed  Google Scholar 

  14. Venning FA, Wullkopf L, Erler JT. Targeting ECM disrupts cancer progression. Front Oncol. 2015;5:224. https://doi.org/10.3389/fonc.2015.00224.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Morra L, Moch H. Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update. Virchows Arch. 2011;459(5):465–75. https://doi.org/10.1007/s00428-011-1151-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wu Q, Fang T, Lang H, Chen M, Shi P, Pang X, et al. Comparison of the proliferation, migration and angiogenic properties of human amniotic epithelial and mesenchymal stem cells and their effects on endothelial cells. Int J Mol Med. 2017;39(4):918–26. https://doi.org/10.3892/ijmm.2017.2897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chassot AA, Le Rolle M, Jourden M, Taketo MM, Ghyselinck NB, Chaboissier MC. Constitutive WNT/CTNNB1 activation triggers spermatogonial stem cell proliferation and germ cell depletion. Dev Biol. 2017;426(1):17–27. https://doi.org/10.1016/j.ydbio.2017.04.010.

    Article  CAS  PubMed  Google Scholar 

  18. Dann CT, Alvarado AL, Molyneux LA, Denard BS, Garbers DL, Porteus MH. Spermatogonial stem cell self-renewal requires OCT4, a factor downregulated during retinoic acid-induced differentiation. Stem Cells. 2008;26(11):2928–37. https://doi.org/10.1634/stemcells.2008-0134.

    Article  CAS  PubMed  Google Scholar 

  19. Zhaleh H, Bidmeshki PA, Azadbakht M. Mesenchymal stem cell condition medium enhanced cell viability in morphine-treated cells. Bratisl Lek Listy. 2020;121(4):263–70. https://doi.org/10.4149/BLL_2020_040.

    Article  CAS  PubMed  Google Scholar 

  20. Ohinata Y, Ohta H, Shigeta M, Yamanaka K, Wakayama T, Saitou M. A signaling principle for the specification of the germ cell lineage in mice. CELL. 2009;137(3):571–84. https://doi.org/10.1016/j.cell.2009.03.014.

    Article  CAS  PubMed  Google Scholar 

  21. Zhao B, Liu JQ, Zheng Z, Zhang J, Wang SY, Han SC, et al. Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways. Cell Tissue Res. 2016;365(1):85–99. https://doi.org/10.1007/s00441-016-2366-1.

    Article  CAS  PubMed  Google Scholar 

  22. Gonzalez-Gonzalez L, Alonso J. Periostin: a matricellular protein with multiple functions in cancer development and progression. Front Oncol. 2018;8:225. https://doi.org/10.3389/fonc.2018.00225.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Murphy-Ullrich JE, Suto MJ. Thrombospondin-1 regulation of latent TGF-beta activation: a therapeutic target for fibrotic disease. Matrix Biol. 2018;68-69:28–43. https://doi.org/10.1016/j.matbio.2017.12.009.

    Article  CAS  PubMed  Google Scholar 

  24. Wu X, Schmidt JA, Avarbock MR, Tobias JW, Carlson CA, Kolon TF, et al. Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc Natl Acad Sci U S A. 2009;106(51):21672–7. https://doi.org/10.1073/pnas.0912432106.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Abofoul-Azab M, AbuMadighem A, Lunenfeld E, Kapelushnik J, Shi Q, Pinkas H, et al. Development of postmeiotic cells in vitro from spermatogonial cells of prepubertal cancer patients. Stem Cells Dev. 2018;27(15):1007–20. https://doi.org/10.1089/scd.2017.0301.

    Article  CAS  PubMed  Google Scholar 

  26. Wang S, Wang X, Wu Y, Han C. IGF-1R signaling is essential for the proliferation of cultured mouse spermatogonial stem cells by promoting the G2/M progression of the cell cycle. Stem Cells Dev. 2015;24(4):471–83. https://doi.org/10.1089/scd.2014.0376.

    Article  CAS  PubMed  Google Scholar 

  27. Sharma M, Braun RE. Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis. DEVELOPMENT. 2018;145(5). https://doi.org/10.1242/dev.151555.

  28. Golestaneh N, Beauchamp E, Fallen S, Kokkinaki M, Uren A, Dym M. Wnt signaling promotes proliferation and stemness regulation of spermatogonial stem/progenitor cells. REPRODUCTION. 2009;138(1):151–62. https://doi.org/10.1530/REP-08-0510.

    Article  CAS  PubMed  Google Scholar 

  29. Takase HM, Nusse R. Paracrine Wnt/beta-catenin signaling mediates proliferation of undifferentiated spermatogonia in the adult mouse testis. Proc Natl Acad Sci U S A. 2016;113(11):E1489–97. https://doi.org/10.1073/pnas.1601461113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF, et al. Interactions between cancer stem cells and their niche govern metastatic colonization. NATURE. 2011;481(7379):85–9. https://doi.org/10.1038/nature10694.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was funded by Shenyang Science and Technology Plan, grant number 20-204-4-31, and National Key Research and Development Program of China, grant number 2016YFC1000600, and The APC was funded by 20-204-4-31.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Tao Zhang or Xining Pang.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, C., Cheng, D., Xu, P. et al. POSTN Promotes the Proliferation of Spermatogonial Cells by Activating the Wnt/β-Catenin Signaling Pathway. Reprod. Sci. 28, 2906–2915 (2021). https://doi.org/10.1007/s43032-021-00596-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-021-00596-1

Keywords

Navigation