ATP-mediated Events in Peritubular Cells Contribute to Sterile Testicular Inflammation

Sci Rep. 2018 Jan 23;8(1):1431. doi: 10.1038/s41598-018-19624-3.


Peritubular myoid cells, which form the walls of seminiferous tubules in the testis, are functionally unexplored. While they transport sperm and contribute to the spermatogonial stem cell niche, specifically their emerging role in the immune surveillance of the testis and in male infertility remains to be studied. Recently, cytokine production and activation of Toll-like receptors (TLRs) were uncovered in cultured peritubular cells. We now show that human peritubular cells express purinergic receptors P2RX4 and P2RX7, which are functionally linked to TLRs, with P2RX4 being the prevalent ATP-gated ion channel. Subsequent ATP treatment of cultured peritubular cells resulted in up-regulated (pro-)inflammatory cytokine expression and secretion, while characteristic peritubular proteins, that is smooth muscle cell markers and extracellular matrix molecules, decreased. These findings indicate that extracellular ATP may act as danger molecule on peritubular cells, able to promote inflammatory responses in the testicular environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Adult
  • Biomarkers / metabolism
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Regulatory Networks*
  • Humans
  • Infertility, Male / immunology
  • Infertility, Male / metabolism*
  • Male
  • Middle Aged
  • Receptors, Purinergic P2X4 / metabolism
  • Receptors, Purinergic P2X7 / metabolism
  • Seminiferous Tubules / immunology
  • Seminiferous Tubules / metabolism*


  • Biomarkers
  • Cytokines
  • Extracellular Matrix Proteins
  • P2RX4 protein, human
  • P2RX7 protein, human
  • Receptors, Purinergic P2X4
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate