{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:49:01Z","timestamp":1794368941229,"version":"4.9.0"},"reference-count":64,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Project of Regional Joint Fund of National Natural Science Foundation of China","award":["U23A20494"],"award-info":[{"award-number":["U23A20494"]}]},{"name":"Key Joint Project of Natural Science Foundation of Chongqing, China","award":["CSTB2024NSCQLZX0142"],"award-info":[{"award-number":["CSTB2024NSCQLZX0142"]}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["CSTB2025NSCQ-GPX0084"],"award-info":[{"award-number":["CSTB2025NSCQ-GPX0084"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>The molecular mechanism underlying male reproductive toxicity associated with Perfluorooctanoic acid (PFOA), a persistent environmental endocrine disruptor (EDC), has not yet been fully elucidated. Six-week-old male C57BL\/6 mice were treated with PFOA by oral gavage at 0, 1.25, 5, 10, and 20 mg\/kg\/day for 35 days to explore its toxic effects on the male reproductive system and the underlying mechanisms. Analyses of semen quality, testicular histopathology, and blood\u2013testis barrier (BTB) integrity revealed that PFOA caused dose-dependent structural and functional damage to the BTB, leading to markedly reduced semen quality. Based on transcriptomic sequencing and differential gene enrichment analysis, the glycolytic pathway was identified as a key regulatory target for PFOA-induced damage to the reproductive system. Further validation revealed that PFOA exposure inhibited glycolysis-related enzymes (Hexokinase 1 (HK1), Glucose Transporter 1 (GLUT1), and Lactate Dehydrogenase A (LDHA)), reduced lactate production and ATP synthesis, lowered Pan-Kla and H3K18la levels, and diminished H3K18la enrichment at the Hk1, Glut1, and Ldha promoters, whereas exogenous sodium lactate reversed these changes. This study is the first to identify the \u201cglycolysis\u2013lactate\u2013H3K18la\u201d chain as a key regulator in PFOA-induced BTB damage and spermatogenesis impairment, offering a new theoretical foundation for understanding EDC-induced male reproductive toxicity.<\/jats:p>","DOI":"10.3390\/toxics14050399","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:39:47Z","timestamp":1778150387000},"page":"399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PFOA Damages Blood\u2013Testis Barrier Integrity in Mice by Inhibited Glycolysis Caused H3K18 Lactylation Modification Impairment"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhengqi","family":"Song","sequence":"first","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Heath, Guizhou Medical University, Guiyang 550025, China"},{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Ruan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Heath, Guizhou Medical University, Guiyang 550025, China"},{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7453-9987","authenticated-orcid":false,"given":"Zhiliang","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Chongqing University of Technology, Chongqing 400054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Heath, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7689-9601","authenticated-orcid":false,"given":"Ziyuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Heath, Guizhou Medical University, Guiyang 550025, China"},{"name":"Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, 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