{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:33Z","timestamp":1785434913591,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"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":"crossref","award":["32573319"],"award-info":[{"award-number":["32573319"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32172803"],"award-info":[{"award-number":["32172803"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32573319"],"award-info":[{"award-number":["32573319"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32172803"],"award-info":[{"award-number":["32172803"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Bisphenol F (BPF), a widespread environmental contaminant and a major substitute for the restricted bisphenol A (BPA), has raised increasing concerns regarding its potential male reproductive health risks, yet its underlying mechanisms remain poorly understood. This study investigates the mechanisms underlying BPF-induced testicular damage, focusing on the interplay among gut microbiota (GM) dysbiosis, histidine metabolism disruption, and ferroptosis. Using a mouse model exposed to BPF (50, 100, and 200 mg\/kg\/day) for 28 days, we observed significant testicular pathology, including seminiferous tubule atrophy, vacuolation, and blood-testis barrier (BTB) impairment. Metagenomic and metabolomic analyses revealed GM dysbiosis and suppressed intestinal histidine metabolism, accompanied by decreased abundance of beneficial taxa (e.g., Bacteroides, Ligilactobacillus) and increased potential pathobionts (e.g., Akkermansia, Mucispirillum). BPF exposure was associated with reduced testicular histidine levels and decreased expression of the histidine transporter-related marker LAT1, suggesting impaired histidine availability and a possible alteration in LAT1\/CD98-mediated transport; however, direct inhibition of LAT1\/CD98 transport activity was not experimentally demonstrated. BPF exposure was accompanied by ferroptosis-related alterations in the testes, including mitochondrial damage, iron accumulation, lipid peroxidation, and downregulation of the xCT-GSH-GPX4 antioxidant axis. In vitro experiments using mouse Sertoli cells (mSCs) confirmed BPF-induced ferroptosis, which was mitigated by the exogenous histidine supplementation. Histidine administration in vivo ameliorated testicular damage, restored BTB integrity, and reversed ferroptotic markers. Our findings support a working model in which a GM\u2013histidine\u2013testis axis may contribute to BPF-induced reproductive toxicity, while further functional studies are required to establish direct causality and transporter-level mechanisms.<\/jats:p>","DOI":"10.3390\/antiox15060714","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:24:33Z","timestamp":1780629873000},"page":"714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota-Mediated Histidine Deficiency Drives Testicular Ferroptosis Induced by Bisphenol F Exposure"],"prefix":"10.3390","volume":"15","author":[{"given":"Bo-Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2503-6061","authenticated-orcid":false,"given":"Dao-Zhen","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Hong","family":"Ji","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fei","family":"Mao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0670-2452","authenticated-orcid":false,"given":"Xue-Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, 5333 Xi-An Road, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1093\/humupd\/dmx022","article-title":"Temporal Trends in Sperm Count: A Systematic Review and Meta-Regression Analysis","volume":"23","author":"Levine","year":"2017","journal-title":"Hum. 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