SAT2 regulates Sertoli cell-germline interactions via STIM1-mediated ROS/WNT/β-catenin signaling pathway

As the main component of seminiferous tubules, Sertoli cells are in close contact with germ cells and generate niche signals, which exhibit pivotal functions in spermatogenesis and male fertility. However, the regulatory mechanisms of Sertoli cell-germline interactions (SGIs) in the testes of neonatal mice (NM) remain largely unclear. Previously, we identified spermidine/spermine N1-acetyl transferase 2 (SAT2) and stromal interaction molecule 1 (STIM1) to be potential regulators of testicular cord formation via comparative proteomics analysis. Here, we demonstrated a novel role of SAT2 for SGIs during testicular development in NM. Testicular explants lacking SAT2 affected the mislocation, but not the quantity, of Sertoli cells, which led to maintenance defects in spermatogonial stem cells (SSCs). Interestingly, SAT2 was essential for the migration of TM4 cells, a Sertoli cell line. Mechanistically, SAT2 was able to bind STIM1, repress its expression, and regulate homeostasis of a reactive oxygen species/wingless type (WNT)/β-catenin pathway in NM testes. Collectively, our study identified that SAT2 was able to regulate SGIs via a STIM1-mediated WNT signaling pathway.