Introduction: Seminal extracellular vesicles support sperm development and influence the female tract immune response. These EVs are thought to be primarily secreted by the prostate(1), but emerging evidence suggests cells throughout the male reproductive tract release EVs.
Methods: EVs secreted by the testis, epididymis, vas deferens, seminal vesicles, and prostate of mice were isolated using differential ultracentrifugation, then characterised using Nanoparticle Tracking Analysis (NTA) (assessing EVs collected from 16 mice), Transmission Electron Microscopy (TEM) and Immunogold labelling (both assessing EVs collected from 4 mice).
Results: NTA revealed fluids from the prostate and seminal vesicles had high concentrations of EVs, while the testis, epididymis (Caput, Corpus and Cauda), and vas deferens fluids were lower. TEM showed variation in EV size with significantly larger EVs (p<0.05) secreted by the seminal vesicles and prostate compared to EVs secreted by the testis, caput, corpus, cauda, and vas deferens. Flotillin-1+ and CD63+ EVs were detected across all male reproductive tract regions using immunogold labelling, with significantly larger (p<0.05) Flotillin-1+ and CD63+ EVs in the testis compared to those secreted from the seminal vesicles, prostate, corpus and cauda. To begin to identify markers for the origins of seminal EVs, immunogold labelling showed the seminal vesicle marker, Mucin-6, in seminal vesicle but not prostate-derived EVs. In contrast, the prostate specific marker Transglutaminase-4 was detected in both seminal vesicle and prostate-derived EV populations.
Conclusions: These data confirm EVs are secreted by cells across the male reproductive tract, potentially contributing to the heterogeneous seminal EV population.