Deoxynivalenol Induces Blood-Testis Barrier Dysfunction through Disrupting p38 Signaling Pathway-Mediated Tight Junction Protein Expression and Distribution in Mice

Deoxynivalenol (DON) is widely presentin cereals and processedgrains. It can disrupt the blood-testicular barrier (BTB), leadingto sterility in males; however, the mechanism is unknown. In thisstudy, 30 Kunming mice and TM4 cells were exposed to 0 or 4.8 mg/kg(28 d) and 0-2.4 & mu;M (24 h) of DON, respectively. Histopathologicalfindings showed that DON increased BTB permeability in mice, leadingto tight junction (TJ) structural damage. Immunofluorescence resultsindicated that DON disrupted the localization of zonula occludens(ZO)-1. The results of protein and mRNA expression showed that theexpression of ZO-1, occludin, and claudin-11 was reduced, and thatthe p38/GSK-3 & beta;/snail and p38/ATF-2/MLCK signaling pathways wereactivated in mouse testes and TM4 cells. Pretreatment with the p38inhibitor SB203580 maintained TJ integrity in TM4 cells after exposureto DON. Thus, DON induced BTB dysfunction in mice by disrupting p38pathway-mediated TJ expression and distribution.