Pathological Characteristics and Mechanisms of Sepsis-Induced Testicular Dysfunction

Sepsis, a serious life-threatening systemic inflammatory disease, has not received enough attention for the testicular dysfunction it causes. The testis is not only a reproductive organ, but also an important endocrine gland that secretes testosterone and other sex hormones. This study aimed to systematically investigate the persistent damage caused by sepsis to testicular function and to explore the underlying mechanisms, with a focus on macrophages. Clinical observations were performed in sepsis patients, and animal experiments were conducted using the cecal ligation and puncture model. Macrophage depletion experiments were further performed to confirm the mechanistic role of macrophages. Clinical observations showed significant low testosterone levels in patients during both acute and recovery phases. In mice, testicular tissue damage and spermatogenic dysfunction occurred at 24 hours post-cecal ligation and puncture and persisted through day 14. Mechanistic studies revealed that sepsis triggers oxidative stress injury by inducing testicular macrophages proliferation and promoting excessive release of pro-inflammatory factors and reactive oxygen species. Macrophage depletion largely abolished sepsis-induced testicular injury. In conclusion, sepsis causes persistent testicular injury through macrophage-associated inflammatory and oxidative stress responses. These findings elucidate the pathogenesis of sepsis-induced testicular injury and identify potential therapeutic targets for improving reproductive-endocrine function and overall prognosis in sepsis patients.