DIA-Based Proteomics Reveals the Protective Effect of Quercetin against Cyclophosphamide-Induced Testicular Toxicity in Mice

Abstract

Cyclophosphamide (CP) is a common employed immunosuppressive and anti-neoplastic alkylating antineoplastic drug with documented male reproductive harm. Quercetin, a widely distributed anti-oxidant flavonoid, has been demonstrated to have a variety of biological roles, including tissue-protective properties. Here, administration of quercetin alleviated the CP-induced damage to the testicles, as evidenced by improvements in body weight, testis and epididymis index, serum testosterone concentration, the pathomorphological of testis, and reduced apoptosis in testicular cells. Moreover, Proteomic data indicated that all DEPs were classified into five categories, Cluster 1 (C1) and C4 were regulated by cyclophosphamide and quercetin. KEGG pathway analyses showed that mTOR signaling pathways and Proteasome were the most abundant pathways in C1 and C4, respectively. In the protein-protein interaction (PPI) network analysis, quercetin inhibits the expression of GSK3B, EIF4E, and RPS6KA2 proteins in CP-induced spermatogenesis failure in mice via the mTOR signaling pathway, protecting against spermatogonia injury. On the other hand, quercetin alleviates spermatogonia injury by stimulating the production of Rps23, Rpl8, Rps11, and Mrps17 proteins in CP-induced testis injury in mice via the pathways of Proteasome. Our results have showed that quercetin has a putative protective effect via modulating the pathways of mTOR and Proteasome in CP induced testis injury