Segment-specific changes with age in the expression of junctional proteinsand the permeability of the blood-epididymis barrier in rats

In aging Brown Norway rats, there is a striking increase in the number of h alo cells in the epididymis; this reflects an activation of the immune syst em. As the brood-epididymis barrier should protect from immunological attac k, we hypothesized that there would be changes in the structure and functio n of this barrier with age. To test this hypothesis, we assessed the immuno cytochemical localization of occludin, ZO-1, and E-cadherin, as well as the lanthanum nitrate permeability of the blood-epididymis barrier, in the epi didymides of Brown Norway rats aged 3, 18,and 24 mo. In the initial segment , occludin, ZO-1, and E-cadherin immunostaining was observed at the apicola teral junction between principal cells in the 3-mo-old animals; with increa sing age, occludin and ZO-1 reactivity decreased, while E-cadherin staining increased along the lateral membrane between principal cells. In the caput , corpus, and cauda epididymidis, occludin, ZO-1, and E-cadherin immunostai ning showed segment-specific and age-dependent differences in their stainin g patterns. The most dramatic changes were seen in the corpus epididymidis with age; the intense E-cadherin cytoplasmic staining that was observed at 3 mo was absent by 24 mo, and no occludin or ZO-1 reactivity was observed i n older animals. The greatest penetration of lanthanum nitrate across the b lood-epididymis barrier and in the lumen was seen in the aging corpus epidi dymidis, while there was no barrier permeability in the initial segment or cauda epididymidis of the aged animals. Taken together, these data indicate that there are segment-specific decreases in the structural and functional integrity of the blood-epididymis barrier with age, most notably in the co rpus epididymidis.