Age-related decline in spermatogenic activity accompanied with endothelial cell senescence in male mice

Male fertility decreases with age, with a reduction of spermatogenesis as one of its causes. Changing of testis environment is suggested as a cause of the phenotype, whereas the mechanisms remain unclear. Here, we investigated the age-related changing in the testicular somatic cells on spermatogenic activity. As mice aged, the number and proliferation activity of spermatogonia significantly reduced. Interestingly, senescence-associated beta-galactosidase-positive cells appeared in testicular endothelial cell (EC) populations but not in germ cells with age. Transcriptome analysis of EC indicated that cellular senescence occurred in the ECs of aged mice. Furthermore, ECs' support capacity for spermatogonial proliferation was significantly decreased with age, whereas the senolytic-induced removal of senescent cells from aged ECs restored their supporting capacity to a comparable level as young ECs. Our data suggest that the accumulation of senescent ECs in the testis is a possible factor contributing to the age-related decline in spermatogenic activity.