Shunde Hospital of Southern Medical University, Shunde, Guangdong, China; State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Stem Cell Reports. 2023 Apr 11;18(4):969-984. doi: 10.1016/j.stemcr.2023.02.011.
The spermatogonial stem cell (SSC) niche is critical for SSC maintenance and subsequent spermatogenesis. Numerous reproductive hazards impair the SSC niche, thereby resulting 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 SSCs (mSSCs). Mechanistically, Lovastatin promotes the self-renewal of mSSCs and inhibits its inflammation and apoptosis through the regulation of isoprenoid intermediates. Remarkably, treatment by Lovastatin could promote the proliferation of undifferentiated spermatogonia in the male gonadotoxicity model generated by busulfan injection. Of note, we demonstrate that Lovastatin could enhance the proliferation of primate undifferentiated spermatogonia. 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 types of male infertility using small compounds.
精原干细胞（SSC）龛对于 SSC 的维持和随后的精子发生至关重要。许多生殖危害会损害 SSC 龛，从而导致 SSC 异常自我更新和男性不育。然而，有前景的针对受损 SSC 龛以促进 SSC 自我更新的药物仍然有限。在这里，我们筛选并评估了洛伐他汀对小鼠 SSCs（mSSCs）自我更新的影响。从机制上讲，洛伐他汀通过调节异戊二烯中间产物促进 mSSC 的自我更新并抑制其炎症和凋亡。值得注意的是，洛伐他汀治疗可促进由白消安注射产生的雄性性腺毒性模型中未分化精原细胞的增殖。值得注意的是，我们证明洛伐他汀可以增强灵长类未分化精原细胞的增殖。总之，我们的研究结果表明，洛伐他汀可以促进鼠和灵长类 SSC 的自我更新，并为使用小分子治疗某些类型的男性不育症提供了依据。
