Targeting SHP-1 to alleviate testicular inflammation and apoptosis in a Poly(I:C)-induced orchitis model.

Abstract

Orchitis, an inflammation of the testes primarily caused by viral infections such as mumps, presents a significant threat to male reproductive health. This study explores the role of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1), a known tumor suppressor, in mitigating inflammation and apoptosis in testicular cells within a model of viral-induced orchitis. To simulate the immune response associated with viral orchitis, we utilized Poly (I:C), a synthetic analog of double-stranded RNA, which mimics the molecular patterns of viral RNA. This model provides a relevant framework for investigating immune responses in the testes triggered by viral-like stimuli. Our research aimed to elucidate the impact of SHP-1 expression on the inflammatory and apoptotic pathways activated during testicular inflammation. We found that Poly (I:C) induced significant inflammation and apoptosis in Leydig and Sertoli cells, characterized by reduced SHP-1 expression and elevated phosphorylated-STAT3 levels. Enhancing SHP-1 expression attenuated these inflammatory and apoptotic responses, whereas reactivating STAT3 with colivelin reversed the suppression of cytokine production and cell death. Moreover, inhibiting SHP-1 with TPI-1 treatment post-Poly (I:C) administration significantly exacerbated testicular inflammation and apoptosis, underscoring SHP-1's critical protective role. These findings highlight the therapeutic potential of targeting SHP-1 and STAT3 pathways in treating orchitis, advancing our understanding of the pathophysiology of testicular inflammation and suggesting new strategies for managing this condition.Author details: Please check if the designated corresponding authors affiliation is correctly identify and amend if necessary. Please see the attached file containing the updated author information for our manuscript. Author names: Please confirm if all the authors names are presented accurately and in the correct sequence. Kindly check and confirm whether the names of all authors has been processed correctly and amend if necessary. Please see the attached file containing the updated author information for our manuscript.