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

Chongyang Wu,Ying Zhang,Qiaoyan Shen,Jinlian Hua,Weishuai Liu,Zhe Zhou

doi:10.18632/oncotarget.12990

Chongyang Wu, Ying Zhang + Show 4 more

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https://doi.org/10.18632/oncotarget.12990

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Abstract

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.

Highlights

Spermatogonial stem cells (SSCs) are the sole adult stem cells in males which transmit genetic and epigenetic information from one generation to the
These showed that C18-4 cells preserved in our laboratory had the typical characteristics of the A single spermatogonial stem cells (SSCs), which was the basis of the experiment
The results indicated that the apoptosis rate was highest in 200 μM Res, reaching 83.6% (Figure 1C)

Summary

Introduction

Spermatogonial stem cells (SSCs) are the sole adult stem cells in males which transmit genetic and epigenetic information from one generation to the next. Spermatogonial stem cells (SSCs) are the sole adult stem cells in males which transmit genetic and epigenetic information from one generation to the In mice, it takes 35 days for a single SSC to generate 1024 sperms [1, 2]. Besides the naturally increased age, there are a large number of drugs, such as busulfan, originally used in chemotherapy, can induce pre-senescence. As a nitrogen mustard alkylating agent, busulfan is widely applied in treatment of chronic myelogenous leukemia and pretreatment of hematopoietic stem cell transplantation. In 1994, Brinster etc. firstly established the azoospermia mice model by busulfan injection, which laid a foundation for the further study in spermatogenesis [11, 12]

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