Peritubular cells of the human testis: prostaglandin E2and more

Background Several layers of slender, smooth muscle-like, peritubular cells and extracellular matrix (ECM) form the peritubular compartment of the human testis. Peritubular cells are the least explored testicular cells. Materials and methods Human testicular peritubular cells (HTPCs) can be isolated from small testicular fragments of patients and studied in vitro. We have used this cellular model, in combination with human testicular samples, to examine how peritubular cells may contribute to male (in)fertility. Results Human testicular peritubular cells (HTPCs) retain contractile abilities in vitro and secrete many proteins. Among them are factors, which serve intra-testicular roles, for example, glial cell line-derived neurotrophic factor (GDNF), thought to be important for the renewal of spermatogonial stem cells (SSCs). Studies in mutant mice indicated that peritubular cell-derivedGDNFis crucial for lifelong spermatogenesis. Thus, peritubular cells are a functional part of theSSCniche. Peritubular cells of mice and men express androgen receptors (AR). In mouse peritubular cells, androgens enhancedGDNFproduction, but not inHTPCs. Rather,ARactivation increased the levels ofARand smooth muscle proteins and thereby enhanced the smooth muscle-like phenotype. Following the lead of a proteomic analysis, which identified the key prostaglandin (PG)-synthesizing enzyme (PTGS1 = COX1), we found thatHTPCs secretePGE(2).COX1, andPGE(2)receptors (EP1, 2, and 4) were identified in peritubular cells in situ, supporting in vivo relevance. InHTPCs, activation ofEP1/4 increasedGDNFand a smooth muscle protein. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), which blocksPGsynthesis. Added toHTPCs it reducedPGE(2)andGDNFproduction and lowered smooth muscle protein levels. If applicable to the in vivo situation, the results suggest that ibuprofen and possibly otherNSAIDs may impair important peritubular cell functions and consequently testicular functions. Conclusion The few examples highlighted, together with others not mentioned here, indicate thatHTPCs provide an experimental window into the human testis.