Effects of age on the structure of the epididymis and on the fertility and progeny outcome in the brown Norway rat

The effects of age on the structure and functions of the epididymis were studied using the Brown Norway rat model. Striking quantitative and qualitative changes during aging in the histology of the epididymis were observed. Characteristic features of aging, such as increases in basement membrane thickness and massive accumulation of lipofuscin, were found. In addition, epididymis-specific signs of aging such as polymorphism of lysosomes, presence of giant vacuoles and spermiophagy, and a major increase in the number of halo cells were also found. The precise nature of halo cells was demonstrated by using specific antibodies. In epididymides from young adult animals, halo cells are composed of three types of immune cells: helper T cells, cytotoxic T cells and monocytes. The three immune cell types present increased with age in the epididymal epithelium in a segment specific manner. In contrast their numbers did not increase significantly in the interstitial tissue. Furthermore, the concentration of cytotoxic T cells and monocytes-macrophages was enhanced in the epididymal epithelium of aged rats whose epididymal lumen contained few spermatozoa. The recruitment of immune cells might be triggered by the accumulation of damaged epithelial cells, or by sperm antigens leaking through the blood epididymis barrier. Thus, the epididymal microenvironment that is essential for the maturation of spermatozoa could be altered in old age. The effect of advancing paternal age on pregnancy and progeny outcomes was assessed by mating Brown Norway male rats of increasing age with young Sprague-Dawley females. The effects of advancing paternal age on the offspring included an increase in preimplantation loss, a decrease in the average fetal weight on day 20 of gestation, and an increase in early neonatal death. These results indicated that the quality of spermatozoa decreases as males age