Protective effects of mouse bone marrow mesenchymal stem cell-derived extracellular vesicles on radiation-induced epididymal cells damage via USP44/RBM14 axis.

BACKGROUND

Radiation-induced damage to reproductive tissues presents a major clinical concern with potentially lasting functional consequences.

METHODS

Here, we investigate the protective function of extracellular vesicles derived from mouse bone marrow mesenchymal stem cells (mBMSCs-EVs) in mitigating ionizing radiation-induced injury in murine epididymal cells (mPC-1).

RESULTS

We demonstrate that mBMSC-EVs significantly enhance cell viability and reduce apoptosis, oxidative stress, and DNA damage in irradiated mPC-1 cells. Besides, we identify the deubiquitinase USP44 as a key mediator enriched in mBMSC-EVs, which confers radioprotection by stabilizing the RNA-binding protein RBM14 through deubiquitination for mPC-1 cells. Silencing USP44 in mBMSCs or their EVs abrogates these protective effects, leading to impaired DNA repair, increased apoptosis, oxidative stress, and disrupted cell cycle progression. Conversely, RBM14 overexpression partially restores cell survival and function, supporting its downstream role in this pathway.

CONCLUSION

Our findings reveal a novel USP44/RBM14 axis mediated by mBMSC-EVs that counteracts radiation injury, and suggest this mechanism as a promising therapeutic approach for protecting reproductive tissues from radiation-induced damage. Notably, these findings are primarily grounded in in vitro experiments utilizing an immortalized epididymal cell line; further in vivo validation and evaluation of clinical translatability are required prior to therapeutic application.