The Presence of Colony-Stimulating Factor-1 and Its Receptor in Different Cells of the Testis; It Involved in the Development of Spermatogenesis In Vitro

Int J Mol Sci. 2021 Feb 26;22(5):2325. doi: 10.3390/ijms22052325.


Spermatogenesis is a complex process, in which spermatogonial cells proliferate and differentiate in the seminiferous tubules of the testis to generate sperm. This process is under the regulation of endocrine and testicular paracrine/autocrine factors. In the present study, we demonstrated that colony stimulating factor-1 (CSF-1) is produced by mouse testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells (such as CDH1-positively stained cells; a marker of spermatogonial cells). In addition, we demonstrated the presence of CSF-1 and its receptor (CSF-1R) in testicular macrophages, Leydig, Sertoli, peritubular cells and spermatogonial cells of human testis. We also show that the protein levels of CSF-1 were the highest in testis of 1-week-old mice and significantly decreased with age (2-12-week-old). However, the transcriptome levels of CSF-1 significantly increased in 2-3-week-old compared to 1-week-old, and thereafter significantly decreased with age. On the other hand, the transcriptome levels of CSF-1R was significantly higher in mouse testicular tissue of all examined ages (2-12-week-old) compared to 1-week-old. Our results demonstrate the involvement of CSF-1 in the induction the proliferation and differentiation of spermatogonial cells to meiotic and postmeiotic stages (BOULE- and ACROSIN-positive cells) under in vitro culture conditions, using methylcellulose culture system (MCS). Thus, it is possible to suggest that CSF-1 system, as a testicular paracrine/autocrine system, is involved in the development of different stages of spermatogenesis and may be used in the development of future therapeutic strategies for treatment of male infertility.

Keywords: Colony stimulating factor-1 (CSF-1); in vitro culture of spermatogonial cells; spermatogenesis; testicular autocrine/paracrine factors; testis.

MeSH terms

  • Animals
  • Humans
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Male
  • Mice
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Spermatogenesis*
  • Testis / cytology
  • Testis / metabolism*


  • CSF1 protein, human
  • CSF1R protein, human
  • Csf1r protein, mouse
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Macrophage Colony-Stimulating Factor