Peritubular Cells The Human Testis Produce PGE2 And May Be Targeted by Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)

FRUNGIERI MB; HERRMANN C; MATZKIN ME; MAYERHOFER A; WINDSCHUETTL S; TIEFENBACHER A; SCHWARZER JU; REY-ARES V; DIETRICH K; EINWANG D; KÖHN FM

Munich

Congreso; LIX Simposio de la Sociedad Alemana de Endrocrinología; 2016

Recent studies have suggested thatblockers of cyclooxygenase-enzymes (COX), namely NSAIDs, may impair humantesticular functions. This implies that prostaglandins (PGs) are produced andmay have favorable actions in the human testis, an organ, which is not readilyaccessible to investigation. We have previously established isolation andculture of human testicular peritubular cells (HTPCs). Little is known aboutthese smooth muscle-like cells, which build the wall of seminiferous tubulesand secrete extracellular matrix (ECM), yet transport of immotile sperm isregarded as a major role. Further roles are emerging, including a contributionto the spermatogonial stem cell (SSC) niche, e.g. via glial derivedneurotrophic factor (GDNF). Our LC-MS/MS analysis of the protein repertoire ofHTPCs has identified a plethora of secreted factors with roles in the testis.The analysis of the cellular proteins of HTPCs revealed COX1 and PGE-synthases.Thus, HTPCs could be a source of PGE2. Consequently, in the human testis theymay be targets for NSAIDs. We started examining these possibilities. Western blots and ELISA measurements confirmed that HTPCs express COX1and that they constitutively secrete PGE2. Immunohistochemistry (IHC) for COX1in human testicular samples revealed in vivo-relevance. The testicularreceptors for PGE2, EP1-4, were examined. EP1, EP2 and EP4 were revealed inHTPCs in vivo and in vitro by RT-PCR and/or IHC. Other testicular cells werealso immunopositive, including Leydig cells. EP3 was detected in spermatogonia,some of which may be SSCs. The results imply interactions of PGE2 withdifferent human testicular cells, yet only some can be directly studied. WhenPGE2 was added to HTPCs it increased the mRNA levels for the contractilityproteins smooth muscle actin and calponin. Thus, PGE2 derived from HTPCs mayfeed back on HTPCs and may be involved in maintaining their contractilephenotype, which is important for sperm transport. The levels of ECM proteinsof the tubular wall, e.g. the proteoglycans decorin and bigylcan, were notaffected by PGE2. HTPCs, like Sertoli cells, produce GDNF, which regulates SSCrenewal and PGE2 decreased its mRNA levels. A surrogate model for human SSCs,TCam-2 (human seminoma cells), expressed EP3, but PGE2 did not alter stem cellmarkers, nor did it affect viability. Thus, in the adult human testis PGE2 isderived from HTPCs and may represent a physiological factor, which contributesto testicular homeostasis. This includes maintenance of the contractilephenotype of peritubular cells and fine-tuning of the SSC niche.