Ginsenoside Rb1 regulates macrophage-spermatocyte crosstalk by targeting the TNF-α/NF-κB/IL-6 axis to alleviate sepsis-induced testicular injury.

Abstract

Sepsis is a multiple organ dysfunction syndrome caused by the dysregulated host response to infection, and this condition could lead to testicular injury and cause male infertility. Testicular macrophages play a key role in testicular injury caused by sepsis. This study focused on the communication mechanism between macrophages and spermatocytes and the role of ginsenoside Rb1 in testicular injury caused by sepsis. We established animal models of sepsis and cell experiments, and applied transcriptome sequencing, flow cytometry, Western blotting and other techniques to explore the related mechanisms in depth. The study found that macrophages were significantly enriched in the testes during sepsis. These macrophages secreted a large amount of IL-6, promoted spermatogenic apoptosis, and exacerbated testicular injury. Rb1 could significantly inhibit LPS-induced spermatocyte apoptosis and reduce the pathological injury of mice testes. Further mechanistic studies revealed that Rb1 directly bound to TNF-α and changed its protein conformation, which blocked the activation of the TNF and NF-κB signaling pathways in macrophages, reduced the secretion of IL-6, thereby inhibiting spermatocyte apoptosis. This study clarified for the first time the new mechanism of IL-6-mediated crosstalk between macrophages and spermatocytes and the unique role of Rb1 therein, providing new ideas and a theoretical basis for the treatment of testicular injury caused by sepsis, and it is expected to improve the reproductive health prognosis of sepsis patients.