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However, there have been few studies on the pathological injury of\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      to the testis and sperm. The NOD-like receptor protein 3 (NLRP3) inflammasome, upon activation, leads to pyroptosis\u2014a 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\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      . This study aimed to investigate whether\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      induced pathological injury of the rabbit testis and sperm through NLRP3 inflammasome-mediated pyroptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      While rabbits in the\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      group received an intratesticular injection of 1 mL of a bacterial suspension containing 10\u2077\/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\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      (MOI\u2009=\u200920). After administering MCC950, the expression levels of the inflammasome NLRP3 and downstream pyroptosis-related molecules were subsequently detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      caused obvious pathological damage to the rabbit testis and sperm reduction. Meanwhile, the gene expression levels of NLRP3, ASC, GSDMD, Caspase-1, IL-I\u03b2, and IL-18 in the\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      group were higher than those of the sham group. Additionally,\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      induced cell injury and pyroptosis in GC-2spd cells, which was improved by the NLRP3 inflammasome inhibitor MCC950.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings validated that\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12865-026-00835-7","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T02:47:08Z","timestamp":1778294828000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treponema pallidum induces pathological injury of the rabbit testis and sperm through NLRP3 inflammasome activation-mediated pyroptosis"],"prefix":"10.1186","volume":"27","author":[{"given":"Tong","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiping","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjie","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingli","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuojun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"835_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02348-0","author":"RW Peeling","year":"2023","unstructured":"Peeling RW, Mabey D, Chen XS, Garcia PJ. 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All procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals (8th edition, National Research Council, USA). Consent to Participate declaration: Not applicable. The rabbits used in this study were purchased from a commercial supplier (Leagene Biotechnology Co., Ltd., Beijing, China). Therefore, informed consent from animal owners was not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"59"}}