Conclusion
UC-MSCs inhibit autophagy and improve sperm quality in AS rats through the AKT/mTOR pathway, highlighting a new idea for the treatment of AS.
Methods
An animal model of AS was established in ORN-induced rats, followed by treatment of UC-MSCs and rapamycin (autophagy activator) or MK-2206 (AKT inhibitor). The sperm motility, concentration, and viability of rats were measured by an automatic sperm analyzer. Hematoxylin and eosin (HE) staining was conducted to observe the pathological injury of testicular tissue in rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was utilized to evaluate the apoptosis rate of testicular cells. Western blot analysis was performed to determine the expression of apoptosis-related proteins, autophagy-related proteins, and AKT, p-AKT, mTOR, and p-mTOR. The rate of light chain 3 (LC3)-positive cells in testicular tissue was detected by immunohistochemistry (IHC).
Objective
Mesenchymal stem cells (MSCs) have been highly confirmed for their critical role in the treatment of different diseases. This study focuses on the mechanism of umbilical cord-derived MSCs (UC-MSCs) in the treatment of ornidazole (ORN)-induced asthenozoospermia (AS) in rats via the AKT/mTOR pathway.
Results
In ORN-induced AS rats, sperm motility, concentration, and viability as well as the number of mesenchymal cells and spermatogenic cells were significantly decreased, spermatogenic tubule space, apoptosis rate, and cleaved caspase-3, LC3II/I, Beclin-1, and LC3-positive cell rates were increased, and Bcl2 was downregulated. UC-MSCs could improve sperm quality and testicular injury in AS rats by inhibiting excessive autophagy. Besides, UC-MSCs could activate the AKT/mTOR pathway. Moreover, inhibition of the AKT/mTOR pathway partially reversed the therapeutic effect of UC-MSCs on ORN-induced AS rats.