{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:48:09Z","timestamp":1788367689433,"version":"build-2803163510"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20212ACB206036"],"award-info":[{"award-number":["20212ACB206036"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012259","name":"Major Discipline Academic and Technical Leaders Training Program of Jiangxi Province","doi-asserted-by":"publisher","award":["20204BCJ22031"],"award-info":[{"award-number":["20204BCJ22031"]}],"id":[{"id":"10.13039\/501100012259","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060278"],"award-info":[{"award-number":["82060278"]}],"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":["82171591"],"award-info":[{"award-number":["82171591"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Environmental Research"],"published-print":{"date-parts":[[2024,4]]},"DOI":"10.1016\/j.envres.2024.118221","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T11:53:34Z","timestamp":1705665214000},"page":"118221","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"special_numbering":"C","title":["Melatonin alleviates di-butyl phthalate (DBP)-induced ferroptosis of mouse leydig cells via inhibiting Sp2\/VDAC2 signals"],"prefix":"10.1016","volume":"247","author":[{"given":"Si","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoju","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-1647","authenticated-orcid":false,"given":"Jiaxiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.envres.2024.118221_bib1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.reprotox.2019.07.017","article-title":"Prenatal exposures to bisphenol A and di (2-ethylhexyl) phthalate disrupted seminiferous tubular development in growing male rats","volume":"88","author":"Abdel-Maksoud","year":"2019","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.envres.2024.118221_bib2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1530\/REP-09-0226","article-title":"Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis: a possible estrogenic effect of di(n-butyl) phthalate","volume":"139","author":"Alam","year":"2010","journal-title":"Reproduction"},{"key":"10.1016\/j.envres.2024.118221_bib3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0009587","article-title":"Specificity protein 2 (Sp2) is essential for mouse development and autonomous proliferation of mouse embryonic fibroblasts","volume":"5","author":"Baur","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.envres.2024.118221_bib4","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1210\/en.2015-1936","article-title":"Prepubertal di-n-butyl phthalate exposure alters sertoli and leydig cell function and lowers bone density in adult male mice","volume":"157","author":"Bielanowicz","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.envres.2024.118221_bib5","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrurol.2017.69","article-title":"Oxidative stress and male infertility","volume":"14","author":"Bisht","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"10.1016\/j.envres.2024.118221_bib6","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tibs.2015.11.012","article-title":"Regulators of iron homeostasis: new players in metabolism, cell death, and disease","volume":"41","author":"Bogdan","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.envres.2024.118221_bib7","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/molehr\/gaz015","article-title":"Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids","volume":"25","author":"Bromfield","year":"2019","journal-title":"Mol. Hum. Reprod."},{"key":"10.1016\/j.envres.2024.118221_bib8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.tox.2017.05.004","article-title":"Prenatal exposure to di-n-butyl phthalate disrupts the development of adult Leydig cells in male rats during puberty","volume":"386","author":"Chen","year":"2017","journal-title":"Toxicology"},{"key":"10.1016\/j.envres.2024.118221_bib9","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/s41556-019-0305-6","article-title":"ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway","volume":"21","author":"Chu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.envres.2024.118221_bib10","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2022.901565","article-title":"Post-translational modification of GPX4 is a promising target for treating ferroptosis-related diseases","volume":"9","author":"Cui","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.envres.2024.118221_bib11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neuroscience.2021.10.013","article-title":"Transcription factor SP2 regulates ski-mediated astrocyte proliferation in vitro","volume":"479","author":"Da","year":"2021","journal-title":"Neuroscience"},{"key":"10.1016\/j.envres.2024.118221_bib12","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.envres.2024.118221_bib13","doi-asserted-by":"crossref","first-page":"561","DOI":"10.4103\/1673-5374.293157","article-title":"Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4","volume":"16","author":"Fan","year":"2021","journal-title":"Neural Regen Res"},{"key":"10.1016\/j.envres.2024.118221_bib14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1182\/blood-2018-05-850404","article-title":"Transferrin receptor 1 controls systemic iron homeostasis by fine-tuning hepcidin expression to hepatocellular iron load","volume":"133","author":"Fillebeen","year":"2019","journal-title":"Blood"},{"key":"10.1016\/j.envres.2024.118221_bib15","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: promise and limitations of antioxidant therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.envres.2024.118221_bib16","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph17165655","article-title":"Critical review on the presence of phthalates in food and evidence of their biological impact","volume":"17","author":"Giuliani","year":"2020","journal-title":"Int. J. Environ. Res. Publ. Health"},{"key":"10.1016\/j.envres.2024.118221_bib17","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.envint.2011.03.005","article-title":"Phthalate metabolites in urine from China, and implications for human exposures","volume":"37","author":"Guo","year":"2011","journal-title":"Environ. Int."},{"key":"10.1016\/j.envres.2024.118221_bib18","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.biocel.2005.08.020","article-title":"Melatonin","volume":"38","author":"Hardeland","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.envres.2024.118221_bib19","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1365-2605.2011.01231.x","article-title":"The endocrine disruptors dibutyl phthalate (DBP) and diethylstilbestrol (DES) influence Leydig cell regeneration following ethane dimethane sulphonate treatment of adult male rats","volume":"35","author":"Heng","year":"2012","journal-title":"Int. J. Androl."},{"key":"10.1016\/j.envres.2024.118221_bib20","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ijheh.2007.07.011","article-title":"Phthalates: toxicology and exposure","volume":"210","author":"Heudorf","year":"2007","journal-title":"Int. J. Hyg Environ. Health"},{"key":"10.1016\/j.envres.2024.118221_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2022.113515","article-title":"Tetramethyl bisphenol a inhibits leydig cell function in late puberty by inducing ferroptosis","volume":"236","author":"Hu","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.envres.2024.118221_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2022.154319","article-title":"Hedyotis diffusa injection induces ferroptosis via the Bax\/Bcl2\/VDAC2\/3 axis in lung adenocarcinoma","volume":"104","author":"Huang","year":"2022","journal-title":"Phytomedicine"},{"key":"10.1016\/j.envres.2024.118221_bib23","doi-asserted-by":"crossref","DOI":"10.3390\/toxins13070495","article-title":"Phthalic acid esters: natural sources and biological activities","volume":"13","author":"Huang","year":"2021","journal-title":"Toxins"},{"key":"10.1016\/j.envres.2024.118221_bib24","doi-asserted-by":"crossref","first-page":"D104","DOI":"10.1093\/nar\/gkaa1057","article-title":"GTRD: an integrated view of transcription regulation","volume":"49","author":"Kolmykov","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.envres.2024.118221_bib25","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/toxsci\/kfi087","article-title":"Subchronic exposure to low concentrations of di-n-butyl phthalate disrupts spermatogenesis in Xenopus laevis frogs","volume":"84","author":"Lee","year":"2005","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.envres.2024.118221_bib26","article-title":"Comparison of the effects of dibutyl and monobutyl phthalates on the steroidogenesis of rat immature leydig cells","volume":"2016","author":"Li","year":"2016","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.envres.2024.118221_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2023.114848","article-title":"Ferroptosis participates in dibutyl phthalate-aggravated allergic asthma in ovalbumin-sensitized mice","volume":"256","author":"Li","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.envres.2024.118221_bib28","volume":"vol. 12","author":"Li","year":"2022"},{"key":"10.1016\/j.envres.2024.118221_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2020.111482","article-title":"Taxifolin attenuates the developmental testicular toxicity induced by di-n-butyl phthalate in fetal male rats","volume":"142","author":"Li","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.envres.2024.118221_bib30","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12958-016-0165-x","article-title":"Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced autophagy of mouse Leydig TM3 cells in vitro","volume":"14","author":"Liu","year":"2016","journal-title":"Reprod. Biol. Endocrinol."},{"key":"10.1016\/j.envres.2024.118221_bib31","article-title":"Effects of ferroptosis on male reproduction","volume":"23","author":"Liu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.envres.2024.118221_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2021.152860","article-title":"Environmentally relevant perinatal exposure to DBP disturbs testicular development and puberty onset in male mice","volume":"459","author":"Ma","year":"2021","journal-title":"Toxicology"},{"issue":"Suppl. 1","key":"10.1016\/j.envres.2024.118221_bib33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1289\/ehp.9366","article-title":"In utero exposure to di(n-butyl) phthalate and testicular dysgenesis: comparison of fetal and adult end points and their dose sensitivity","volume":"115","author":"Mahood","year":"2007","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.envres.2024.118221_bib34","doi-asserted-by":"crossref","first-page":"11920","DOI":"10.1074\/jbc.M112.433847","article-title":"Voltage-dependent anion channels modulate mitochondrial metabolism in cancer cells: regulation by free tubulin and erastin","volume":"288","author":"Maldonado","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.envres.2024.118221_bib35","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/360313a0","article-title":"Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice","volume":"360","author":"Matzuk","year":"1992","journal-title":"Nature"},{"key":"10.1016\/j.envres.2024.118221_bib36","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.bbamem.2011.10.005","article-title":"VDAC isoforms in mammals","volume":"1818","author":"Messina","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.envres.2024.118221_bib37","doi-asserted-by":"crossref","first-page":"13911","DOI":"10.1074\/jbc.M313589200","article-title":"Sp2 DNA binding activity and trans-activation are negatively regulated in mammalian cells","volume":"279","author":"Moorefield","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.envres.2024.118221_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2021.101947","article-title":"NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases","volume":"41","author":"Park","year":"2021","journal-title":"Redox Biol."},{"key":"10.1016\/j.envres.2024.118221_bib39","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1158\/0008-5472.CAN-03-3730","article-title":"Identification of Sp2 as a transcriptional repressor of carcinoembryonic antigen-related cell adhesion molecule 1 in tumorigenesis","volume":"64","author":"Phan","year":"2004","journal-title":"Cancer Res."},{"key":"10.1016\/j.envres.2024.118221_bib40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1289\/ehp.824527","article-title":"Hepatic effects of phthalate esters","volume":"45","author":"Seth","year":"1982","journal-title":"Environ. Health Perspect."},{"key":"10.1016\/j.envres.2024.118221_bib41","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.envres.2024.118221_bib42","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/5080843","article-title":"Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis","author":"Su","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.envres.2024.118221_bib43","doi-asserted-by":"crossref","first-page":"7844","DOI":"10.1093\/nar\/gks544","article-title":"Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes","volume":"40","author":"Terrados","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.envres.2024.118221_bib44","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10815-014-0344-7","article-title":"Iron and copper in male reproduction: a double-edged sword","volume":"32","author":"Tvrda","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"10.1016\/j.envres.2024.118221_bib45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40659-019-0248-1","article-title":"Role of JNK and ERK1\/2 MAPK signaling pathway in testicular injury of rats induced by di-N-butyl-phthalate (DBP)","volume":"52","author":"Wang","year":"2019","journal-title":"Biol. Res."},{"key":"10.1016\/j.envres.2024.118221_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2023.121434","article-title":"Cadmium exposure during puberty damages testicular development and spermatogenesis via ferroptosis caused by intracellular iron overload and oxidative stress in mice","volume":"325","author":"Wang","year":"2023","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.envres.2024.118221_bib47","doi-asserted-by":"crossref","first-page":"42791","DOI":"10.1021\/acsami.2c00707","article-title":"p53 promotes ferroptosis in macrophages treated with Fe(3)O(4) nanoparticles","volume":"14","author":"Wu","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"10.1016\/j.envres.2024.118221_bib48","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1074\/jbc.M109.078881","article-title":"Sp2 is a maternally inherited transcription factor required for embryonic development","volume":"285","author":"Xie","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.envres.2024.118221_bib49","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/tox.23081","article-title":"Ginsenoside Rg1 ameliorates reproductive function injury in C57BL\/6J mice induced by di-N-butyl-phthalate","volume":"36","author":"Xu","year":"2021","journal-title":"Environ. Toxicol."},{"key":"10.1016\/j.envres.2024.118221_bib50","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41467-020-14324-x","article-title":"Nedd4 ubiquitylates VDAC2\/3 to suppress erastin-induced ferroptosis in melanoma","volume":"11","author":"Yang","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.envres.2024.118221_bib51","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.toxlet.2016.01.016","article-title":"DBP-induced endoplasmic reticulum stress in male germ cells causes autophagy, which has a cytoprotective role against apoptosis in vitro and in vivo","volume":"245","author":"Zhang","year":"2016","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.envres.2024.118221_bib52","doi-asserted-by":"crossref","DOI":"10.1016\/j.etap.2019.103236","article-title":"The role of ANXA5 in DBP-induced oxidative stress through ERK\/Nrf 2 pathway","volume":"72","author":"Zhang","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."}],"container-title":["Environmental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0013935124001257?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0013935124001257?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T05:08:59Z","timestamp":1766725739000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0013935124001257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":52,"alternative-id":["S0013935124001257"],"URL":"https:\/\/doi.org\/10.1016\/j.envres.2024.118221","relation":{},"ISSN":["0013-9351"],"issn-type":[{"value":"0013-9351","type":"print"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Melatonin alleviates di-butyl phthalate (DBP)-induced ferroptosis of mouse leydig cells via inhibiting Sp2\/VDAC2 signals","name":"articletitle","label":"Article Title"},{"value":"Environmental Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.envres.2024.118221","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"118221"}}