Lovastatin Promotes the Self-renewal of Murine and Primate Spermatogonial Stem Cells

The spermatogonial stem cells (SSCs) niche is critical for SSC maintenance and the subsequent spermatogenesis. Numerous reproductive hazards impair the SSC niche, thereby result in aberrant SSC self-renewal and male infertility. However, promising agents targeting the impaired SSC niche to promote SSC self-renewal are still limited. Here, we screen out and assess the effects of Lovastatin on the self-renewal of mouse spermatogonial stem cells (mSSCs). Mechanistically, Lovastatin promotes the self-renewal of mSSCs and inhibits its inflammation and apoptosis through the regulation of isoprenoid intermediates. Likewise, other statins exhibit similar effects on SSC self-renewal. Remarkably, the treatment by Lovastatin could promote the self-renewal of mSSCs in the male gonadotoxicity model generated by busulfan injection. Noteworthy, we demonstrate that Lovastatin could significantly enhance the self-renewal of in vitro cultured primate SSCs. Collectively, our findings uncover that lovastatin could promote the self-renewal of both murine and primate SSCs and have implications for the treatment of certain male infertility using small compounds. Overall design: We screen out and assess the effects of Lovastatin on the self-renewal of mouse spermatogonial stem cells (mSSCs). To investigate how lovastatin functioned in mSSC self-renewal, we performed bulk RNA-Seq using cell samples from PTC, LOVA, and NTC groups. Mechanistically, Lovastatin promotes the self-renewal of mSSCs and inhibits its inflammation and apoptosis through the regulation of isoprenoid intermediates.