摘要
Seminal plasma is a rich source of proteins and serves as an ideal sample for proteomic analysis of male infertility.In varicoceleassociated in fertility,the contributory role of semi nal plasma proteins specific to un ilateral and bilateral varicocele is not clear.Furthermore,there is a lack of specific protein biomarker to differentiate bilateral from unilateral varicocele.The main objective is to identify the differentially regulated molecular and cellular pathways in bilateral varicocele?Furthermore,we intend to identify seminal plasma biomarkers to differentiate bilateral and unilateral varicocele patients in comparison with fertile healthy men.Global proteomic an alysis of seminal plasma protei ns has identified the function ality of d iff ere ntially expressed proteins(DEPs)in varicocele patients.Bioinformatic analysis has revealed response to reactive oxygen species and oxidative stress,and tissue homeostasis as top process pathways that are affected in bilateral varicocele patients compared to fertile healthy men.In comparison with unilateral varicocele patients,inflammatory response pathways were dysregulated,especially interleukin 6(IL-6)signaling and Janus kinasesignal transducer and activator of transcription(Jak?STAT)pathways,in bilateral varicocele patients,owing to the involvement of underexpressed DEPs.Key DEPs associated with oxidative stress(peroxiredoxin 2;PRDX2),DNA fragmentation(fatty acid synthase;FASN),and inflammatory resp onse(fibr on ectin 1;FN1)validated by western blot analysis revealed differential expressi on of these proteins in unilateral and bilateral varicocele groups.Altered expression of DEPs and its association with key processes show that the seminal plasma homeostasis is compromised in bilateral varicocele patients?Furthermore,we propose PRDX2,FASN,and FN1 as potential noninvasive seminal plasma markers for the differentiation of unilateral and bilateral varicocele patients.