Age-related decline in spermatogenic activity accompanied with endothelial cell senescence in male mice
Manabu Ozawa,
Hideto Mori,
Tsutomu Endo,
Yu Ishikawa-Yamauchi,
Daisuke Motooka,
Chihiro Emori,
Masahiro Ikawa
Affiliations
Manabu Ozawa
Laboratory of Reproductive Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Corresponding author
Hideto Mori
Laboratory of Reproductive Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Tsutomu Endo
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Yu Ishikawa-Yamauchi
Laboratory of Reproductive Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Daisuke Motooka
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Chihiro Emori
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Masahiro Ikawa
Laboratory of Reproductive Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Corresponding author
Summary: Male fertility decreases with aging, with spermatogenic decline being one of its causes. Altered testis environment is suggested as a cause of the phenotype; however, the associated mechanisms remain unclear. Herein, we investigated the age-related changes in testicular somatic cells on spermatogenic activity. The number and proliferation of spermatogonia significantly reduced with aging in mice. Interestingly, senescence-associated β-galactosidase-positive cells appeared in testicular endothelial cell (EC) populations, but not in germ cell populations, with aging. Transcriptome analysis of ECs indicated that senescence occurred in the ECs of aged mice. Furthermore, the support capacity of ECs for spermatogonial proliferation significantly decreased with aging; however, the senolytic-induced removal of senescent cells from aged ECs restored their supporting capacity to a comparable level as that of young ECs. Our results suggest that the accumulation of senescent ECs in the testis is a potential factor contributing to the age-related decline in spermatogenic activity.
