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Background <p><i>Treponema pallidum</i> (<i>T. pallidum</i>) can invade various organs and tissues. However, there have been few studies on the pathological injury of <i>T. pallidum</i> to the testis and sperm. The NOD-like receptor protein 3 (NLRP3) inflammasome, upon activation, leads to pyroptosis—a programmed, pro-inflammatory cell death process, and promotes inflammatory responses. Previous investigations have found that the NLRP3 inflammasome is elevated in the testis tissues of rabbits infected with <i>T. pallidum</i>. This study aimed to investigate whether <i>T. pallidum</i> induced pathological injury of the rabbit testis and sperm through NLRP3 inflammasome-mediated pyroptosis.</p> Methods <p>While rabbits in the <i>T. pallidum</i> group received an intratesticular injection of 1 mL of a bacterial suspension containing 10⁷/mL treponemes, those in the sham group were administered an equal volume of normal saline to serve as the injection procedure control. 14 days later, testis tissues were harvested for IHC and H&amp;E staining, and analysis of qPCR. In vitro, GC-2spd cells were stimulated by <i>T. pallidum</i> (MOI = 20). After administering MCC950, the expression levels of the inflammasome NLRP3 and downstream pyroptosis-related molecules were subsequently detected.</p> Results <p><i>T. pallidum</i> caused obvious pathological damage to the rabbit testis and sperm reduction. Meanwhile, the gene expression levels of NLRP3, ASC, GSDMD, Caspase-1, IL-Iβ, and IL-18 in the <i>T. pallidum</i> group were higher than those of the sham group. Additionally, <i>T. pallidum</i> induced cell injury and pyroptosis in GC-2spd cells, which was improved by the NLRP3 inflammasome inhibitor MCC950.</p> Conclusions <p>Our findings validated that <i>T. pallidum</i> induced pathological damage to the testis and sperm reduction via NLRP3 inflammasome activation and pyroptosis. By specifically inhibiting the NLRP3 inflammasome, MCC950 has the potential to ameliorate sperm cell damage under in vitro conditions via the blockade of pyroptotic cell death.</p>

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Treponema pallidum induces pathological injury of the rabbit testis and sperm through NLRP3 inflammasome activation-mediated pyroptosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Tong Zheng,
  • Meiping Ye,
  • Yilan Yang,
  • Linxin Yao,
  • Danyang Zou,
  • Chunjie Liao,
  • Xin Feng,
  • Tingli Tian,
  • Zhuojun Tang,
  • Pingyu Zhou

摘要

Background

Treponema pallidum (T. pallidum) can invade various organs and tissues. However, there have been few studies on the pathological injury of T. pallidum to the testis and sperm. The NOD-like receptor protein 3 (NLRP3) inflammasome, upon activation, leads to pyroptosis—a programmed, pro-inflammatory cell death process, and promotes inflammatory responses. Previous investigations have found that the NLRP3 inflammasome is elevated in the testis tissues of rabbits infected with T. pallidum. This study aimed to investigate whether T. pallidum induced pathological injury of the rabbit testis and sperm through NLRP3 inflammasome-mediated pyroptosis.

Methods

While rabbits in the T. pallidum group received an intratesticular injection of 1 mL of a bacterial suspension containing 10⁷/mL treponemes, those in the sham group were administered an equal volume of normal saline to serve as the injection procedure control. 14 days later, testis tissues were harvested for IHC and H&E staining, and analysis of qPCR. In vitro, GC-2spd cells were stimulated by T. pallidum (MOI = 20). After administering MCC950, the expression levels of the inflammasome NLRP3 and downstream pyroptosis-related molecules were subsequently detected.

Results

T. pallidum caused obvious pathological damage to the rabbit testis and sperm reduction. Meanwhile, the gene expression levels of NLRP3, ASC, GSDMD, Caspase-1, IL-Iβ, and IL-18 in the T. pallidum group were higher than those of the sham group. Additionally, T. pallidum induced cell injury and pyroptosis in GC-2spd cells, which was improved by the NLRP3 inflammasome inhibitor MCC950.

Conclusions

Our findings validated that T. pallidum induced pathological damage to the testis and sperm reduction via NLRP3 inflammasome activation and pyroptosis. By specifically inhibiting the NLRP3 inflammasome, MCC950 has the potential to ameliorate sperm cell damage under in vitro conditions via the blockade of pyroptotic cell death.