Mesenchymal Stem Cell-derived Extracellular Vesicles for Male Infertility: Mechanisms and Potential

A BSTRACT Male infertility contributes to nearly half of all infertility cases worldwide and arises from diverse etiologies, including oxidative stress, inflammation, endocrine disruption, and environmental exposures. Current treatment strategies, particularly assisted reproductive technologies, are often limited in their ability to restore normal spermatogenesis. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach in regenerative medicine. These vesicles carry a diverse cargo of proteins, lipids, and nucleic acids that can modulate cellular signaling pathways involved in testicular repair and spermatogenesis. This mini-review provides an overview of the biological characteristics of MSC-EVs, elaborates on their molecular mechanisms in male infertility, summarizes key findings from preclinical models, and discusses their translational potential and current challenges. MSC-EVs offer a novel therapeutic paradigm with improved safety and feasibility compared to stem cell-based therapies.