Seminal plasma exosomes and male infertility: current progress and future directions

Male infertility remains a major global health concern. Conventional semen analysis offers limited explanatory power, with most cases remaining idiopathic, underscoring the urgent need for novel biomarkers and mechanisms. Exosomes, 30–150 nm extracellular vesicles that transfer proteins, RNAs, and bioactive molecules, have emerged as pivotal regulators of male reproductive function. Epididymosomes promote sperm maturation and capacitation by delivering proteins and antioxidants. Prostasomes act post-ejaculation, supporting capacitation, the acrosome reaction, and immune protection within the female reproductive tract. Testicular exosomes regulate early spermatogenesis, particularly by modulating spermatogonial stem-cell proliferation and differentiation. Seminal-vesicle exosomes influence motility and fertilization, while bulbourethral exosomes may modulate seminal pH, ion balance, and viscosity. Dysregulation of these exosomal pathways has been linked to oligozoospermia, asthenozoospermia, and teratozoospermia. This review integrates mechanistic and translational evidence across seminal plasma exosome subtypes, emphasizes their reproductive functions, and highlights their diagnostic and therapeutic potential, offering a foundation for exosome-based precision medicine in male infertility.