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Our results showed that PFHxS\u2010treated mice have significant reproductive toxicity, including a decrease in sperm count and motility, and the levels of sex hormones (<jats:italic>P<\/jats:italic> &lt; 0.05). Concurrently, structural abnormalities are observed in sperm, affecting \u224860\u201375% of those in the PFHxS\u2010treated group. Additionally, it is found that the structure of the blood\u2010testis barrier (BTB) is damaged after PFHxS treatment, leading to higher expression levels of inflammatory cytokines in the microenvironment for spermatogenesis. Moreover, the expression of proteins associated with mitochondrial biogenesis, including PTEN\u2010induced kinase 1 (PINK1) and NADPH oxidase 4 (NOX4), is dysregulated in the testes after PFHxS treatment. Based on metabolome data, the differential metabolite 3\u2010hydroxybutanoic acid is identified in the PFHxS\u2010treated group, which can regulate the histone Kac levels, especially H3K4ac and H3K9ac. In summary, the results of this study suggest that in the testes of PFHxS\u2010treated mice, inflammatory factors disrupt the mitochondrial function and metabolic profiles and hinder the progress of gene transcription through histone Kac, ultimately causing sperm dysfunction.<\/jats:p>","DOI":"10.1002\/advs.202409383","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T15:34:31Z","timestamp":1737128071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Perfluorohexane Sulfonic Acid Disrupts the Immune Microenvironment for Spermatogenesis by Damaging the Structure of the Blood\u2010Testis Barrier in Mice"],"prefix":"10.1002","volume":"12","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"},{"name":"Department of Epidemiology, School of Public Health Nantong University  Nantong 226001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxue","family":"Shu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Shan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoqiao","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-9188","authenticated-orcid":false,"given":"Chuncheng","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg9065"},{"key":"e_1_2_10_2_1","volume":"55","author":"Ng C.","year":"2021","journal-title":"Environ. 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