Myotubularin related protein 7 is essential for the spermatogonial stem cell homeostasis via PI3K/AKT signaling

Myotubularin related protein 7 (MTMR7), a key member of the MTMR family, depicts phosphatase activity and is involved in myogenesis and tumor growth. We have previously identified MTMR7 in the proteomic profile of mouse spermatogonial stem cell (SSC) maturation and differentiation, implying that MTMR7 is associated with neonatal testicular development. In this study, to further explore the distribution and function of MTMR7 in mouse testis, we studied the effect of Mtmr7 knockdown on neonatal testicular development by testicular and SSC culture methods. Our results revealed that MTMR7 is exclusively located in early germ cells. Deficiency of MTMR7 by morpholino in neonatal testis caused excessive SSC proliferation, which was attributable to the aberrant PI3K/AKT signaling activation. Altogether, our study demonstrates that MTMR7 maintains SSC homeostasis by inhibiting PI3K/AKT signaling activation.肌管蛋白相关蛋白7（Myotubularin related protein 7, MTMR7）是MTMR家族的关键成员，具有磷酸酶活性，参与肌发生与肿瘤生长过程。我们此前在小鼠精原干细胞（spermatogonial stem cell, SSC）成熟与分化的蛋白质组谱中鉴定到MTMR7，提示其与新生小鼠睾丸发育相关。本研究为进一步探究MTMR7在小鼠睾丸中的分布与功能，采用睾丸组织与精原干细胞培养方法，分析了Mtmr7敲低对新生小鼠睾丸发育的影响。结果显示，MTMR7特异性定位于早期生殖细胞；通过吗啉代寡核苷酸敲低新生小鼠睾丸内的MTMR7，会引发精原干细胞过度增殖，该现象归因于PI3K/AKT信号通路的异常激活。综上，本研究证实MTMR7通过抑制PI3K/AKT信号通路激活，维持精原干细胞的稳态平衡。