Segment-Specific Changes with Age in the Expression of Junctional Proteins and the Permeability of the Blood-Epididymis Barrier in Rats1

Abstract

In aging Brown Norway rats, there is a striking increase in the number of halo cells in the epididymis; this reflects an activation of the immune system. As the blood-epididymis barrier should protect from immunological attack, we hypothesized that there would be changes in the structure and function of this barrier with age. To test this hypothesis, we assessed the immunocytochemical localization of occludin, ZO-1, and E-cadherin, as well as the lanthanum nitrate permeability of the blood-epididymis barrier, in the epididymides 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 apico-lateral junction between principal cells in the 3-mo-old animals; with increasing 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 immunostaining showed segment-specific and age-dependent differences in their staining 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 in older animals. The greatest penetration of lanthanum nitrate across the blood-epididymis barrier and in the lumen was seen in the aging corpus epididymidis, 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 corpus epididymidis.