Resveratrol changes spermatogonial stem cells (SSCs) activity and ameliorates their loss in busulfan-induced infertile mouse

The decline of quantity and quality of sperm are correlated with the increasing age and some anti-cancer compounds such as busulfan. Previous studies have shown that Resveratrol (Res) inhibits tumorigenesis and metastasis of many cancers including mammary tumor, prostate and pancreatic cancers. It acts as anti-age in mouse and human, however, little is known about its protective effect on aged spermatogonial stem cells (SSCs). Here, we investigated the effects of Res in vitro on SSCs using C18-4 cells and in vivo in busulfan-induced azoospermia mice model. The results showed that Res at different concentrations had different effects on C18-4 cells. Treatment with 2 μM of Res promotes cell proliferation and inhibits apoptosis, but stimulates apoptosis with a higher concentration (20 μM) in C18-4 cells. Using busulfan-induced infertility mice model, we demonstrated that Res (30 mg/kg/d and 100 mg/kg/d) clearly ameliorated SSC loss to recover the spermatogenesis. Taken together, our data suggest that Res might be an approach for therapeutic intervention to promote SSC proliferation and cease SSC loss in azoospermia mice model induced by busulfan.