Exposure of DBP in gestation induces inflammation of testicular Sertoli cells in progeny by activating NLRP3 inflammasomes

摘要

Di-n-butyl phthalate (DBP), as one of the environmental chemicals, can cause male reproductive decline including testicular hypoplasia and impairments of spermatogenesis. Testicular inflammation is positively related to decline in male reproductive function. However, whether exposure to DBP in utero can cause testicular inflammation in progeny has not been studied. In this study, we established an animal model and observed that DBP exposure during gestation induced testicular inflammation in progeny with the increased expression of proinflammatory cytokines and chemokines including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and CXC chemokine ligand-10 (CXCL-10), representing the activation of the nuclear factor kappa B (NF-κB). However, NF-κB was activated within 1 h in Sertoli cells (SCs) when exposed to MBP (a metabolite of DBP) in vitro. Meanwhile, we detected increased expression of inflammatory NLR family pyrin domain containing 3 (NLRP3), resulting from Pellino2-mediated NLRP3 inflammasome priming. Further, we confirmed that the activation of the NLRP3/caspase-1/IL-1β canonical inflammasome pathway induced secretion of inflammatory factors of SCs and immune response, and INF39 (an inhibitor of NLRP3) could inhibit the inflammation in vitro. Collectively, these findings indicated that NLRP3 inflammasomes played key roles in DBP-induced inflammation in testicular SCs.