New insights into the molecular mechanisms of 1,3-dinitrobenzene-induced testicular toxicity

Several studies have shown that 1,3-dinitrobenzene (DNB) causes injury to Sertoli cells and induces apoptosis in the surrounding germinal cells in male laboratory rats ; however, the mechanisms by which DNB functions are not well understood. In this context, we have conducted studies using standard parameters and molecular tools to better understand the pathogenesis of the testicular effects produced by DNB, as well as its mode of action. Wistar rats were orally exposed to 0.1-8 mg DNB/kg/day for 4 days. Testosterone concentrations were not affected at any dose level, but marked histopathological lesions in the testes were recorded at 4 mg/kg/day. Global transcriptomic analysis of rat testes revealed cell cycle and cell death as the major biological processes affected. In particular, we identified an alteration in the expression of genes associated with cell cycle progression (mitotic roles of polo-like kinase). Dinitrobenzene was administered in suspension to rats (7 weeks old at start of treatment) by oral gavage at a daily dose of 0 (control, 0.5% methylcellulose in sterilized water), 0.1, 1, and 4 mg/kg body weight, for 4 consecutive days. Dose-related changes in gene expression were determined in the testes using whole genome oligonucleotide microarrays.