Lipopolysaccharide induces epididymal and testicular antimicrobial gene expression in vitro: insights into the epigenetic regulation of sperm-associated antigen 11e gene

Abstract

Infections of the male reproductive tract lead to infertility, and the molecular mechanisms that operate under these conditions are not well studied. Using epididymal and testicular tissues cultured in vitro, we demonstrate that lipopolysaccharide (LPS) induces the mRNA expression of beta-defensins, Spag11s, and pro-inflammatory cytokines in the rat caput, cauda, and testes. LPS-induced antimicrobial gene expression involved NF-kB activation and decreased levels of histone deacetylase 1 (HDAC1) and DNA methyltransferase (DNMT), all of which possibly allow antimicrobial gene transcription. Inhibition of endogenous HDAC1 and DNMT1 resulted in higher antimicrobial gene expression when compared to the LPS alone treated conditions. Increased trimethylation of histone 3, its binding to the upstream region of Spag11e gene, and demethylation of this region were observed during endotoxin challenge. We demonstrate that antimicrobial gene expression in the male reproductive tract tissues during endotoxin challenge involves NF-kB activation and epigenetic changes.