{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:11:39Z","timestamp":1787029899701,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103880"],"award-info":[{"award-number":["82103880"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373609"],"award-info":[{"award-number":["82373609"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304107"],"award-info":[{"award-number":["82304107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82103880"],"award-info":[{"award-number":["82103880"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82373609"],"award-info":[{"award-number":["82373609"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82304107"],"award-info":[{"award-number":["82304107"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Key Laboratory of fire Protection and Retardant Technology, Ministry of Emergency Management","award":["FHZR2023KFMS_02"],"award-info":[{"award-number":["FHZR2023KFMS_02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Nano-antimony trioxide (Nano-Sb2O3) is extensively utilized in industrial production and consumer products, leading to widespread environmental contamination and human exposure. Accumulating evidence has demonstrated that Nano-Sb2O3 induces male reproductive toxicity, yet the underlying molecular mechanisms remain poorly understood. In this study, male C57BL\/6 mice were exposed to Nano-Sb2O3 (2.5, 5.0, and 7.5 mg\/kg\/day). Exposure to Nano-Sb2O3 induced dose-dependent reproductive toxicity, evidenced by dose-dependent reductions in sperm motility (56.70% to 36.10%) and sperm density (15.76 \u00d7 106\/mL to 2.79 \u00d7 106\/mL) and a marked elevation in sperm malformation rates (4.56% to 44.36%), as well as severe histopathological alterations, testicular Sb accumulation, and elevated reactive oxygen species (ROS) levels. Transcriptomic analysis revealed significant enrichment of the PPAR and PI3K-Akt signaling pathways and identified SPP1 as one of the most significantly differentially expressed genes. Computational pathway perturbation analyses further yielded hypothesis-generating evidence supporting the potential involvement of PPAR signaling suppression and PI3K-Akt and inflammatory pathway activation following Nano-Sb2O3 exposure. Both mRNA and protein levels of SPP1 were significantly upregulated in a dose-dependent manner in mouse testes and TM4 Sertoli cells. In vitro experiments further demonstrated that Nano-Sb2O3 increased the expression of pro-inflammatory cytokines IL-1\u03b2 and IL-6 by up to 5.6-fold and 4.7-fold, respectively, while impairing Sertoli cell viability and wound-healing capacity. Importantly, Spp1 silencing attenuated inflammatory responses and restored the expression of blood\u2013testis barrier (BTB)-associated proteins, including ZO-1, Claudin-11, and N-cadherin. These findings suggest that SPP1 may contribute to Nano-Sb2O3-induced inflammatory responses and alterations in BTB-associated proteins, thereby potentially participating in male reproductive injury.<\/jats:p>","DOI":"10.3390\/toxics14070569","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spp1 Contributes to Nano-Antimony Trioxide-Induced Male Reproductive Toxicity Associated with Inflammatory Response and Blood\u2013Testis Barrier-Related Alterations"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8479-7728","authenticated-orcid":false,"given":"Zhenyao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China"},{"name":"Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9893-0972","authenticated-orcid":false,"given":"Yiwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1795-6491","authenticated-orcid":false,"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"First School of Clinical Medicine, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jin","sequence":"additional","affiliation":[{"name":"Medical Biological Experiment Credit Center, Basic Medical College, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fire Protection and Retardant Technology, Ministry of Emergency Management, Chengdu 610036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bano, S., Husain, F.M., Khan, R.A., Alsalme, A., and Siddique, J.A. 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