The mechanisms behind testicular aging are poorly understood. Previous studies suggest that the testicular microenvironment is more affected by age than the male germ cell lineage. Here we analyze male reproductive aging using a unique xenografting approach. By exposing young and aged mice to newborn hamster testicular tissue, we can explore (a) whether the development and endocrine activity of hamster testicular grafts and the initiation of stem cell activity within them are affected by age of the recipients and (b) whether the endocrine response to the xenografted hamster tissue varies with recipient age. Newborn Djungarian hamster (Phodopus sungorus) testes were grafted into young (12 weeks) and aged (1 year) adult castrated nude mice. We also analyzed intact and castrated young and old control groups. After 13 weeks, 100 grafts were recovered from a total of 15 recipients and were histologically analyzed. Anatomical and endocrine parameters were recorded for each recipient as well as for the controls. Xenografted recipients responded with a normalization of their endocrine and anatomical parameters to an extent typical for their age. Although recipient age did not significantly affect graft survival and size, histopathological changes as well as spermatogenic damage within the grafts were more pronounced in the young recipients (56% Sertoli-cell-only tubules vs. 32% in the old recipients). We conclude from our data that the androgen-related changes associated with male reproductive aging are not primarily controlled by the testis. We speculate that the better development of testicular grafts in aged recipients may be owing to immunosenescence.
Aging Animals