Skip to main content
SpringerLink
Log in

Expression of Insulin-like Growth Factor Binding Protein-3 and Regulation of the Insulin-like Growth Factor-I Axis in Pig Testis

  • Research Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

The stem cell niche is a complex unit comprising key components, such as the extracellular matrix and various paracrine factors, which regulate the differentiation of adult stem cells. In our previous study, we established pig spermatogonial stem cells (pSSCs) in culture and identified the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in pSSCs. The present study investigated not only the expression of IGFBP-3, but also its possible role in pSSCs. In this study, IGFBP-3-expressing cells responded positively to protein gene product 9.5 (PGP9.5), which is a marker for pig spermatogonia. IGFBP-3 expression was significantly increased in 60-dayold pig testes. Additionally, the expression levels of insulinlike growth factor I (IGF-I) and its receptor (IGF-IR) were observed in pSSCs and pig Sertoli cells (pSCs). Furthermore, IGF-I treatment enhanced the proliferation of pSCs and pSSCs when they were co-cultured. Blocking the IGF-I pathway using a specific IGF-IR inhibitor dramatically reduced the proliferation of pSCs. In addition, when heparan sulfate was used to sequester IGFBP-3 from IGF-I binding, a significant increase in the proliferation of pSCs was observed. Exogenous IGF-I treatment also increased the expression level of IGFBP-3 in cultured pSSCs. Furthermore, pSSCs grew well in IGF-I-treated pSC conditioned media. In summary, IGF-I and IGF-IR signaling are important for the proliferation of pSCs, and the germ cell-derived IGFBP-3 had an inhibitory effect on the mitotic activity of IGF-I in pSCs.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Luo, J., S. Megee, R. Rathi, and I. Dobrinski (2006) Protein gene product 9.5 is a spermatogonia-specific marker in the pig testis: application to enrichment and culture of porcine spermatogonia. Mol. Reprod. Dev. 73: 1531–1540.

    Article  CAS  PubMed  Google Scholar 

  2. Goel, S., M. Sugimoto, N. Minami, M. Yamada, S. Kume, and H. Imai (2007) Identification, isolation, and in vitro culture of porcine gonocytes. Biol. Reprod. 77: 127–137.

    Article  CAS  PubMed  Google Scholar 

  3. Goel, S., M. Fujihara, N. Minami, M. Yamada, and H. Imai (2008) Expression of NANOG, but not POU5F1, points to the stem cell potential of primitive germ cells in neonatal pig testis. Reproduction 135: 785–795.

    Article  CAS  PubMed  Google Scholar 

  4. Lee, K. H., W. Y. Lee, J. H. Kim, M. J. Yoon, N. H. Kim, J. H. Kim, S. J. Uhm, D. H. Kim, H. J. Chung, and H. Song (2013) Characterization of GFRa-1-positive and GFRa-1-negative spermatogonia in neonatal pig testis. Reprod. Domest. Anim. 48: 954–960.

    Article  CAS  PubMed  Google Scholar 

  5. Kim, Y. H., B. J. Kim, B. G. Kim, Y. A. Lee, K. J. Kim, H. J. Chung, S. Hwang, J. S. Woo, J. K. Park, J. A. Schmidt, M. G. Pang, and B. Y. Ryu (2013) Stage-specific embryonic antigen-1 expression by undifferentiated spermatogonia in the prepubertal boar testis. J. Anim. Sci. 91: 3143–3154.

    Article  CAS  PubMed  Google Scholar 

  6. Lee, W. Y., K. H. Lee, Y. T. Heo, N. H. Kim, J. H. Kim, J. H. Kim, S. H. Moon, H. J. Chung, M. J. Yoon, and H. Song (2014) Transcriptional coactivator undifferentiated embryonic cell transcription factor 1 expressed in spermatogonial stem cells: a putative marker of boar spermatogonia. Anim. Reprod. Sci. 150: 115–124.

    Article  CAS  PubMed  Google Scholar 

  7. Wang, X., T. Chen, Y. Zhang, B. Li, Q. Xu, and C. Song (2015) Isolation and culture of pig spermatogonial stem cells and their in vitro differentiation into neuron-like cells and adipocytes. Int. J. Mol. Sci. 16: 26333–26346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lee, W. Y., J. T. Do, C. Park, J. H. Kim, H. J. Chung, K. W. Kim, C. H. Gil, N. H. Kim, and H. Song (2016) Identification of putative biomarkers for the early stage of porcine spermatogonial stem cells using next-generation sequencing. PLoS One 11: e0147298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pitetti, J. L., P. Calvel, C. Zimmermann, B. Conne, M. D. Papaioannou, F. Aubry, C. R. Cederroth, F. Urner, B. Fumel, M. Crausaz, M. Docquier, P. L. Herrera, F. Pralong, M. Germond, F. Guillou, B. Jégou, and S. Nef (2013) An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice. Mol. Endocrinol. 27: 814–827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lin, T., J. Haskell, N. Vinson, and L. Terracio (1986) Direct stimulatory effects of insulin-like growth factor-I on Leydig cell steroidogenesis in primary culture. Biochem. Biophys. Res. Commun. 137: 950–956.

    Article  CAS  PubMed  Google Scholar 

  11. Söder, O., P. Bang, A. Wahab, and M. Parvinen (1992) Insulinlike growth factors selectively stimulate spermatogonial, but not meiotic, deoxyribonucleic acid synthesis during rat spermatogenesis. Endocrinology 131: 2344–2350.

    Article  PubMed  Google Scholar 

  12. Escott, G. M., A. P. Jacobus, and E. S. Loss (2013) PI3K-dependent actions of insulin and IGF-I on seminiferous tubules from immature rats. Pflugers Arch. 465: 1497–1505.

    Article  CAS  PubMed  Google Scholar 

  13. Cohen, P. (2006) Insulin-like growth factor binding protein-3:insulin-like growth factor independence comes of age. Endocrinology 147: 2109–2111.

    Article  CAS  PubMed  Google Scholar 

  14. Smith, E. P., L. Lu, S. D. Chernausek, and D. J. Klein (1994) Insulinlike growth factor-binding protein-3(IGFBP-3) concentration in rat Sertoli cell-conditioned medium is regulated by a pathway involving association of IGFBP-3 with cell surface proteoglycans. Endocrinology 135: 359–364.

    Article  CAS  PubMed  Google Scholar 

  15. Rappaport, M. S. and E. P. Smith (1995) Insulin-like growth factor (IGF) binding protein 3 in the rat testis: follicle-stimulating hormone dependence of mRNA expression and inhibition of IGF-I action on cultured Sertoli cells. Biol. Reprod. 52: 419–425.

    Article  CAS  PubMed  Google Scholar 

  16. Wang, D., M. L. Nagpal, S. Shimasaki, N. Ling, and T. Lin (1995) Interleukin-1 induces insulin-like growth factor binding protein-3 gene expression and protein production by Leydig cells. Endocrinology 136: 4049–4055.

    Article  CAS  PubMed  Google Scholar 

  17. Lee, W. Y., H. J. Park, R. Lee, K. H. Lee, Y. H. Kim, B. Y. Ryu, N. H. Kim, J. H. Kim, J. H. Kim, S. H. Moon, J. K. Park, H. J. Chung, D. H. Kim, and H. Song (2013) Establishment and in vitro culture of porcine spermatogonial germ cells in low temperature culture conditions. Stem Cell Res. 11: 1234–1249.

    Article  CAS  PubMed  Google Scholar 

  18. Lee, K. H., W. Y. Lee, J. H. Kim, C. K. Park, J. T. Do, J. H. Kim, Y. S. Choi, N. H. Kim, and H. Song (2016) Subculture of germ cell-derived colonies with GATA4-positive sertoli cells from neonatal pig testes. Stem Cells Int. 2016: 6029271.

    PubMed  PubMed Central  Google Scholar 

  19. Fu, Z., T. Kubo, T. Noguchi, and H. Kato (2001) Developmental changes in the mRNA levels of IGF-I and its related genes in the reproductive organs of Japanese quail (Coturnix coturnix japonica). Growth Horm. IGF Res. 11: 24–33.

    Article  CAS  PubMed  Google Scholar 

  20. Antich, M., E. Fabian, J. Sarquella, and L. Bassas (1995) Effect of testicular damage induced by cryptorchidism on insulin-like growth factor I receptors in rat Sertoli cells. J. Reprod. Fertil. 104: 267–275.

    Article  CAS  PubMed  Google Scholar 

  21. Hansson, H. A., H. Billig, and J. Isgaard (1989) Insulin-like growth factor I in the developing and mature rat testis: immunohistochemical aspects. Biol. Reprod. 40: 1321–1328.

    Article  CAS  PubMed  Google Scholar 

  22. Jia, Y., K. W. Lee, R. Swerdloff, D. Hwang, L. J. Cobb, A. Sinha Hikim, Y. H. Lue, P. Cohen, and C. Wang (2010) Interaction of insulin-like growth factor-binding protein-3 and BAX in mitochondria promotes male germ cell apoptosis. J. Biol. Chem. 285: 1726–1732.

    Article  CAS  PubMed  Google Scholar 

  23. Richardson, L. L., H. K. Kleinman, and M. Dym (1995) Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro in the rat. Biol. Reprod. 52: 320–330.

    Article  CAS  PubMed  Google Scholar 

  24. Borland, K., K. E. Muffly, and P. F. Hall (1986) Production of components of extracellular matrix by cultured rat Sertoli cells. Biol. Reprod. 35: 997–1008.

    Article  CAS  PubMed  Google Scholar 

  25. Beattie, J., M. Kreiner, G. J. Allan, D. J. Flint, D. Domingues, and C. F. van der Walle (2009) IGFBP-3 and IGFBP-5 associate with the cell binding domain (CBD) of fibronectin. Biochem. Biophys. Res. Commun. 381: 572–576.

    Article  CAS  PubMed  Google Scholar 

  26. Hodgkinson, S. C., J. R. Napier, G. S. Spencer, and J. J. Bass (1994) Glycosaminoglycan binding characteristics of the insulinlike growth factor-binding proteins. J. Mol. Endocrinol. 13: 105–112.

    Article  CAS  PubMed  Google Scholar 

  27. Arai, T., A. Parker, W. Jr. Busby, and D. R. Clemmons (1994) Heparin, heparan sulfate, and dermatan sulfate regulate formation of the insulin-like growth factor-I and insulin-like growth factorbinding protein complexes. J. Biol. Chem. 269: 20388–20393.

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Stem Cells and Regenerative Technology, KIT, Konkuk University, Seoul, 05029, Korea

    Hyun-Jung Park, Seung-Yeon Chai, Hyuk Song & Kwonho Hong

  2. Department of Beef & Dairy Science, Korea National College of Agriculture and Fisheries, Jeonbuk, 54874, Korea

    Won-Young Lee

  3. Animal Biotechnology Divisions, National Institute of Animal Science, RDA, Wanju, 55365, Korea

    Jae-Seok Woo & Hak-Jae Chung

  4. Department of Swine & Poultry Science, Korea National College of Agriculture and Fisheries, Jeonbuk, 54874, Korea

    Jin-Ki Park

Authors
  1. Hyun-Jung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Won-Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seung-Yeon Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jae-Seok Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hak-Jae Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin-Ki Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hyuk Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kwonho Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kwonho Hong.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, HJ., Lee, WY., Chai, SY. et al. Expression of Insulin-like Growth Factor Binding Protein-3 and Regulation of the Insulin-like Growth Factor-I Axis in Pig Testis. Biotechnol Bioproc E 23, 278–285 (2018). https://doi.org/10.1007/s12257-018-0041-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-018-0041-y

Keywords

Search

Navigation