Is Emerging Nanomedicine a Friend or Foe to Germ Cells?

Nanomaterials are increasingly applied in biomedicine and have significant potential in reproductive medicine. However, because they can impact germ cells, use of nanomaterials could represent a "double-edged sword", whose benefits must be balanced with the possible risks. Because of their excellent physicochemical properties, nanoparticles (NPs) can serve as multi-functional platforms for targeted drug delivery, enhancing outcomes in assisted reproductive technologies, refining in vitro culture systems, and improving the precision of diagnostic imaging. Nevertheless, accumulating evidence indicates that various NPs, including metallic and polymeric forms, can accumulate in reproductive tissues and induce detrimental effects, primarily through increased oxidative stress, DNA damage, and activation of apoptotic pathways. Moreover, NPs can directly compromise gamete quality and function: in oocytes, NP exposure can disrupt key processes, such as meiotic spindle assembly and chromosomal segregation; while in sperm, NPs can impair critical functions, such as histone-to-protamine exchange and mitochondrial integrity. The delicate balance between the benefits and risks of NP use are profoundly influenced by their physicochemical properties. This review critically assesses the "friend or foe" duality of NP use in reproductive medicine, by systematically analyzing their beneficial applications in contrast with their potential for NP-induced toxicity. Mechanistic pathways of NP toxicity are described, and the necessity of a safety-focused approach for the future development of reproductive nanomedicine is emphasised.