睾丸组织微环境的改变是影响精子质量，导致男性生育力下降的重要因素，成为全球共同关注和研究的热点。然而，何种类型细胞如何参与精子发生过程至今仍不明确，亟待阐明。申请人前期证实了新生或成年小鼠睾丸内存在睾丸间质干细胞(SLCs)，将其移植于老年小鼠体内，不仅可以分化为睾丸间质细胞、分泌睾酮、促进精子发生的减数分裂过程，还促进精子发生的有丝分裂过程，发挥了睾酮以外的作用，显著提高老年小鼠的生育能力。表达谱测序显示SLCs高表达细胞衰老相关细胞因子Osteopontin等，提示该细胞可能直接参与了生精微环境的调节。据此，本研究拟利用体内外模型、基因干扰、重组蛋白及Osteopontin基因敲除小鼠等方法，探讨SLCs对睾丸微环境，以及生精过程的影响及机制。通过上述研究，对睾丸微环境有新的认识，同时为阐释精子发生的机制提供新的调控机理，为研发新型维持生育力的方法提供可靠的理论依据。

Testicular microenvironment plays an important role in spermatogenesis. Dysfunction of the testicular microenvironment can induce or alter the progression of sperm quality and male fertility. However, it is still unclear which type of cells participates in which specific process of spermatogenesis. Our previous studies have shown that stem Leydig cells (SLCs) located the testicular interstitial compartment in the neonatal or adult mice, when transplanted into aged male mice, the SLCs differentiate into mature Leydig cells, produce testosterone and promote meiosis of spermatogenesis. Moreover, SLCs can promote mitosis of spermatogenesis, and thus significantly improve the fertility of aged male mice, indicating an effect beyond testosterone. RNA sequencing analysis showed that Osteopontin, cellular aging regulating cytokine, is highly expressed in SLCs. Taken together, these results suggest that SLCs might directly participate in the regulation of spermatogenesis. Here, we explore the mechanism in which SLCs modulate spermatogenesis and testicular microenvironment by in vitro and in vivo models, gene interference, Osteopontin protein and Osteopontin knockout mice model. Taken together, this study provides a novel modulating mechanism of spermatogenesis, understanding of the testicular microenvironment，and also a reliable theoretical basis for the research and development of maintenance on male fertility.