Prostaglandin E2 (PGE2) is a testicular peritubular cell-derived factor involved in human testicular homeostasis

REY, V; KÖHN FM; FRUNGIERI MB; ROSSI SP; SCHWARZER JU; MAYERHOFER A; DIETRICH K; WELTER H

Munich

Congreso; 50th Annual Conference of Physiology and Pathology of Reproduction and 42th Mutual Conference of Veterinary and Human Reproductive Medicine; 2017

In the testis, smooth muscle-like peritubular cells build the wall of seminiferous tubules. Transport of immotile sperm to the rete testis has been regarded as their major role. We have established a culture procedure for human testicular peritubular cells (HTPCs) and a subsequent proteome-analysis of HTPCs has revealed among others cyclooxygenase 1 (COX1) and 2 PGE-synthases (PTGES2 and 3). This implies that HTPCs are a source of PGE2, which consequently may be a physio logical factor in the human testis. Western blots confi rmed that HTPCs express COX1 and ELISA-measurements showed that they constitutively secrete PGE2. Indomethacin, a prototype non-steroidal anti-infl ammatory drug (NSAID), signifi cantly reduced PGE2 synthesis. Immunohistochemistry(IHC) showed COX1 and specifi c receptors for PGE2, EP1?4 in human testicular samples. EP1, EP2 and EP4 were revealed in HTPCs in vivo and in vitro by RT-PCR and/or IHC. Results of collagen gel contraction assay indicate that PGE2 does not acutely contract HTPCs, yet qPCR studies showed that it increased the mRNA levels for the contractility proteins, smooth muscle actin (SMA) and calponin in a concentration- depended manner. HTPCs, like Sertoli cells, produce glial derived neurotrophic factor (GDNF), which regulates the renewal of spermatogonial stem cells (SSCs). PGE2 increasedGDNF mRNA and GNDF levels in the culture medium. Thus, HTPCs are sourcesof PGE2, which may contribute to testicular homeostasis. This includes maintenanceof the contractile phenotype of peritubular cells and, via GDNF, a fi ne tuning of theSSC niche. Blockage of PG-production e.g. by NSAIDs, steroids or other substances maythus have unwanted testicular side effects.