A novel effect of polychlorinated biphenyls: impairment of the tight junctions in the mouse epididymis.

Polychlorinated biphenyls (PCBs) exhibit a broad range of adverse biological effects, including reproductive toxicity. However, the mechanisms by which PCBs disrupt the epididymis remain obscure. We analyzed the gene expression profile in mice epididymis exposed to PCBs (Aroclor 1254) at doses comparable to human exposure using a cDNA microarray. Differentially expressed genes were involved in a variety of function categories and biological pathways, including GTP binding, nucleosome assembly, and ribosome and protein disulfide isomerase. The differentially expressed genes related to GTP binding were highly enriched. The abundance of GTP binding proteins related to tight junctions being reduced and the phosphorylation level of their downstream effectors were impaired after exposure to PCBs. The results of tracer studies demonstrated that the permeability of blood-epididymis barrier was increased by PCB exposure. In addition, PCB exposure also disrupted the expression of the tight junction proteins, zonula occludens-1 and occludin. We demonstrated for the first time that exposure to PCBs at doses relevant for the general population was able to affect the blood-epididymis barrier in mice through altering GTP binding and tight junction proteins. Our results provided a novel insight into the molecular mechanisms linking PCB exposure to sperm maturation.