Testicular peritubular cells the human testis produce PGE2 and may be a target for non-steroidal anti-inflammatory drugs (NSAIDs).

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

San Diego

Congreso; 49th Annual Meeting of the Society for the Study of Reproduction; 2016

Recent studies suggested that NSAIDs i.e. blockers of cyclooxygenase-enzymes (COX) impair human testicular functions. This implies favorable actions of prostaglandins (PGs) in the human testis, an organ, which is not readily accessible to investigation. We have previously established isolation and culture of human testicular peritubular cells (HTPCs). These smooth muscle-like cells secrete extracellular matrix (ECM) proteins and build the wall of seminiferous tubules. An LC-MS/MS analysis of the proteins of HTPCs has among others identified COX1 and PGE-synthases. This implies that they are a source of PGE2 and that HTPCs may be targets for NSAIDs. We started examining these possibilities. Western blots and ELISA measurements confirmed that HTPCs express COX1 and secrete PGE2. Immunohistochemistry (IHC) for COX1 of human testicular samples revealed in vivo-relevance. The receptors for PGE2 were examined by RT-PCR and IHC. EP1, EP2 and EP4 were found in HTPCs in vivo and in vitro. Other testicular cells were also immunoreactive, including Leydig cells. EP3 localized to spermatogonia, some of which may be spermatogonial stem cells. The results imply interactions of PGE2 with several testicular cells, yet only some can be directly studied. When PGE2 was added to HTPCs we observed concentration-dependent consequences, which varied between cells derived from individual men. In general, qPCR studies revealed that PGE2 increased the mRNA levels for contractility proteins (smooth muscle actin (SMA), calponin). Thus PGE2 may be involved in maintaining the contractile phenotype of HTPCs. PGE2 did not affect the levels of ECM proteins decorin and biglycan. Thus, in the adult human testis PGE2 is, at least in part, derived from HTPCs. It may represent a physiological factor, which via its receptors, influences testicular cells and contributes to testicular homeostasis.