Background: Cattle fertility has been in decline for the past 20 years. Small extracellular vesicles (sEVs) are cell-secreted nanoparticles (~30 – 150 nm diameter) present in biofluids such as blood plasma and have been used as biomarkers of health and disease. As essential players in cell-cell signalling and communication, sEVs provide a systemic snapshot of the overall health state of the animal. Immune dysregulation is associated with poor reproductive outcomes in cattle; therefore, our lab has investigated whether proteomic analysis of circulating (blood plasma-derived) sEVs by mass spectrometry (MS) is a valid tool for profiling cattle with known immune diversity due to tick burden.
Methods: Blood was collected into evacuated EDTA blood tubes from cattle with low (>200 ticks) or high tick resistance (no identifiable ticks) (n = 3/group). sEVs were isolated from blood plasma by sequential centrifugation and size exclusion chromatography using an established method of sEV isolation. sEV and non-sEV containing fractions were pooled separately and subjected to validation experiments prior to being processed for MS analysis operated in data-dependent acquisition mode. Data were processed using Protein Pilot and filtered using 1% false discovery rate (FDR) cut-off at the protein level, and 5% FDR at the peptide level, with minimum 2 peptides per protein. PANTHERGO online software tool was utilised for gene ontology analysis from the final protein list.
Results: A total of 490 unique sEV proteins were identified. Of the 30 proteins unique to high tick-resistant cattle, defense/immunity proteins accounted for 50% of these, however this protein class was not detected in low tick-resistant animals.
Conclusions: Proteome profiling of circulating sEVs is a valid tool for assessing immune status in cattle. Blood plasma-derived sEV profiling may be of use in determining cattle at-risk of immune dysfunction around the time of calving with the aim of improving reproductive outcomes.