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

Abstract

In man, blockage of prostaglandin (PG)-production e.g. by non-steroidal anti-inflammatory drug (NSAIDs) may have negative testicular side effects, implying beneficial actions of PGs in the testis. We examined human testicular samples and isolated human testicular peritubular cells (HTPCs) to explore sites of PG-synthesis and targets. HTPCs express cyclooxygenase 1 (COX1) and secrete PGE₂. Receptors (EP1, 2, 4) were specifically identified in peritubular cells. In HTPCs PGE₂ significantly increased mRNA levels of the contractility protein calponin, but did not induce contractions. PGE₂, as well as EP1 and EP4 receptor agonists, significantly increased glia cell line derived neurotrophic factor (GDNF) mRNA and/or protein levels. Importantly, the NSAID ibuprofen reduced PGE₂ and this action also lowered SMA and calponin mRNA levels and levels of secreted GDNF protein. The results reveal an unknown PGE₂ system in the human testis, in involving peritubular cells, which may be prone to interference by NSAIDs.

Keywords: Anti-inflammatory drugs; GDNF; Male fertility; Male infertility; Testis.