{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:52:23Z","timestamp":1792151543655,"version":"4.4.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130094"],"award-info":[{"award-number":["82130094"]}],"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":["82304185"],"award-info":[{"award-number":["82304185"]}],"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":["82504434"],"award-info":[{"award-number":["82504434"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dietary patterns orchestrate systemic metabolism and reproductive health, yet whether specific dietary patterns modulate susceptibility to ozone-induced male reproductive toxicity and its intergenerational consequences remains unclear. Here, male C57BL\/6J mice were fed ad libitum (AL), a 30% calorie-restricted diet (CR), or a 45% high-fat diet (HFD), followed by ozone exposure (1 ppm, 4 h\/day, 5 days\/week for 3 months) to recapitulate real-world condition. We found that ozone exposure exacerbated reproductive injury under both CR and HFD, each diet perturbing metabolism through distinct pathways. Under CR, ozone further suppressed glycolysis, the TCA cycle, and amino acid metabolism, resulting in severe testicular energy depletion and impaired spermatogenic differentiation. In contrast, HFD amplified ozone-induced metabolic overload, inflammatory activation, and mitochondrial stress, accompanied by dysregulated lipid metabolism. Integrated metabolomic analyses identified disruption of the glucose-lactate-TCA axis as a central mechanism underlying testicular energy failure. Furthermore, exposed males (F0) were subsequently mated with unexposed females to generate offspring (F1 and F2) for assessment of next-generation health risks. The results showed that paternal dietary regimen and ozone exposure exclusively perturbed metabolic homeostasis in F1 offspring, indicating a reversible metabolic reprogramming rather than stable transgenerational inheritance. Collectively, these findings establish systemic metabolic status as a critical determinant of ozone-induced reproductive toxicity and reveal that paternal nutritional and environmental challenges jointly prime metabolic susceptibility in the next generation (F1).<\/jats:p>","DOI":"10.1021\/envhealth.5c00865","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:54:00Z","timestamp":1780394040000},"page":"2219-2231","source":"Crossref","is-referenced-by-count":0,"title":["Dietary Patterns\nModulate Ozone-Induced Reproductive\nInjury in C57BL\/6J Mice"],"prefix":"10.1021","volume":"4","author":[{"given":"Yuzhi","family":"Guo","sequence":"first","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-4492","authenticated-orcid":true,"given":"Shen","family":"Chen","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahan","family":"Yang","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhu","family":"Ye","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohuan","family":"Gui","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2578-3369","authenticated-orcid":true,"given":"Guanghui","family":"Dong","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9725-5530","authenticated-orcid":true,"given":"Daochuan","family":"Li","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5435-1664","authenticated-orcid":true,"given":"Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Sun Yat-sen University , , ,","place":["Guangzhou, China, 510080"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"issue":"10258","key":"2026101607062300800_cit1","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/S0140-6736(20)30752-2","article-title":"Global Burden of 87 Risk Factors in 204 Countries and\nTerritories, 1990\u20132019: A Systematic Analysis for the Global\nBurden of Disease Study 2019","volume":"396","author":"GBD 2019 Risk Factors Collaborators.","year":"2020","journal-title":"Lancet"},{"issue":"12","key":"2026101607062300800_cit2","doi-asserted-by":"publisher","first-page":"e958","DOI":"10.1016\/S2542-5196(22)00260-1","article-title":"Global Trends in Ozone\nConcentration and Attributable Mortality for Urban, Peri-Urban, and\nRural Areas between 2000 and 2019: A Modelling Study","volume":"6","author":"Malashock","year":"2022","journal-title":"Lancet Planet. Health."},{"key":"2026101607062300800_cit3","doi-asserted-by":"publisher","DOI":"10.1021\/envhealth.5c00617","article-title":"Long-Term Ambient Ozone\nExposure and Nonaccidental Mortality among Chinese Adults: A Nationwide\nCohort Study","author":"Zou","year":"2026","journal-title":"Environ. Health"},{"issue":"4","key":"2026101607062300800_cit4","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1164\/rccm.202107-1599OC","article-title":"Long-Term Ozone Exposure\nand Small Airway Dysfunction: The China Pulmonary Health (CPH) Study","volume":"205","author":"Niu","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026101607062300800_cit5","doi-asserted-by":"publisher","first-page":"137577","DOI":"10.1016\/j.jhazmat.2025.137577","article-title":"Effects\nof Co-Exposure to Heat and Ozone on\nLipid Metabolism in the Liver and Adipose Tissue of C57BL\/6J Male\nMice","volume":"489","author":"Jiang","year":"2025","journal-title":"J. Hazard. Mater."},{"issue":"10","key":"2026101607062300800_cit6","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1021\/envhealth.4c00066","article-title":"Ambient Ozone Exposure,\nSemen Plasma Metabolites, and Sperm Quality Decline among Adult Men\nin Wuhan, China","volume":"2","author":"Zhang","year":"2024","journal-title":"Environ. Health"},{"key":"2026101607062300800_cit7","unstructured":"Brooke, H.; Jeffrey, D. H.; Erin, H.\n          Integrated Science Assessment\n(ISA) for Ozone and Related Photochemical Oxidants; U.S. Environmental Protection Agency, 2020."},{"key":"2026101607062300800_cit8","doi-asserted-by":"publisher","first-page":"132292","DOI":"10.1016\/j.jhazmat.2023.132292","article-title":"Ozone Exposure Associates with Sperm Quality\nIndicators: Sperm Telomere Length as a Potential Mediating Factor","volume":"459","author":"Lu","year":"2023","journal-title":"J. Hazard. Mater."},{"issue":"6558","key":"2026101607062300800_cit9","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3002","article-title":"Prenatal\nMaternal Infection\nPromotes Tissue-Specific Immunity and Inflammation in Offspring","volume":"373","author":"Lim","year":"2021","journal-title":"Science"},{"issue":"7931","key":"2026101607062300800_cit10","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41586-022-05274-z","article-title":"Prenatal Immune Stress Blunts Microglia\nReactivity, Impairing Neurocircuitry","volume":"610","author":"Hayes","year":"2022","journal-title":"Nature"},{"issue":"1","key":"2026101607062300800_cit11","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1038\/s41467-024-45675-4","article-title":"Multigenerational\nPaternal Obesity Enhances\nthe Susceptibility to Male Subfertility in Offspring via WT1 N6-Methyladenosine\nModification","volume":"15","author":"Xiong","year":"2024","journal-title":"Nat. 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Fibre Toxicol."},{"issue":"1","key":"2026101607062300800_cit14","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12989-023-00526-w","article-title":"Type 1 Diabetes and Diet-Induced Obesity Predispose\nC57BL\/6J Mice\nto PM2.5-Induced Lung Injury: A Comparative Study","volume":"20","author":"Chen","year":"2023","journal-title":"Part. Fibre Toxicol."},{"key":"2026101607062300800_cit15","doi-asserted-by":"publisher","first-page":"107808","DOI":"10.1016\/j.envint.2023.107808","article-title":"Periconceptional\nMaternal Diet Quality Influences Blood\nHeavy Metal Concentrations and Their Effect on Low Birth Weight: The\nJapan Environment and Children\u2019s Study","volume":"173","author":"Okubo","year":"2023","journal-title":"Environ. 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Rev. Endocrinol."},{"issue":"6","key":"2026101607062300800_cit22","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1001\/jamainternmed.2016.1189","article-title":"Effect of Calorie Restriction\non Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese\nAdults: The CALERIE 2 Randomized Clinical Trial","volume":"176","author":"Martin","year":"2016","journal-title":"JAMA Intern. Med."},{"issue":"2","key":"2026101607062300800_cit23","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1007\/s13679-024-00557-0","article-title":"Effects of Calorie\nRestriction on Preserving Male Fertility, Particularly\nin a State of Obesity","volume":"13","author":"Zafar","year":"2024","journal-title":"Curr. Obes. Rep."},{"issue":"5","key":"2026101607062300800_cit24","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1016\/j.cmet.2025.03.001","article-title":"Intermittent Fasting\nBoosts Sexual Behavior by Limiting the Central Availability of Tryptophan\nand Serotonin","volume":"37","author":"Xie","year":"2025","journal-title":"Cell Metab."},{"key":"2026101607062300800_cit25","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1146\/annurev-pathmechdis-051222-015350","article-title":"Immune Dysregulation\nin Obesity","volume":"20","author":"Jiang","year":"2025","journal-title":"Annu. Rev. Pathol."},{"key":"2026101607062300800_cit26","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.3389\/fimmu.2018.02649","article-title":"Inflammatory\nLinks between High-Fat\nDiets and Diseases","volume":"9","author":"Duan","year":"2018","journal-title":"Front. Immunol."},{"issue":"8","key":"2026101607062300800_cit27","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41585-024-00866-y","article-title":"Signatures\nof Metabolic\nDiseases on Spermatogenesis and Testicular Metabolism","volume":"21","author":"Carrageta","year":"2024","journal-title":"Nat. Rev. Urol."},{"issue":"6","key":"2026101607062300800_cit28","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrurol.2012.77","article-title":"Metabolic\nRegulation\nIs Important for Spermatogenesis","volume":"9","author":"Rato","year":"2012","journal-title":"Nat. Rev.\nUrol."},{"issue":"7","key":"2026101607062300800_cit29","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.tem.2004.07.003","article-title":"Lactate and Energy\nMetabolism in Male Germ Cells","volume":"15","author":"Boussouar","year":"2004","journal-title":"Trends Endocrinol.\nMetab."},{"issue":"19","key":"2026101607062300800_cit30","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e38591","article-title":"Energy Metabolism and\nSpermatogenesis","volume":"10","author":"Rotimi","year":"2024","journal-title":"Heliyon"},{"key":"2026101607062300800_cit31","doi-asserted-by":"publisher","first-page":"118897","DOI":"10.1016\/j.ecoenv.2025.118897","article-title":"Maternal Liver Lipid\nDysregulation Mediates Fetal Developmental Impairments Induced by\nGestational Co-Exposure to Ozone and Heat in C57BL\/6J Mice","volume":"303","author":"Guo","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026101607062300800_cit32","doi-asserted-by":"publisher","first-page":"138049","DOI":"10.1016\/j.jhazmat.2025.138049","article-title":"Subchronic Ozone Exposure\nLeads to Multi-Organ Injuries with Differential Reversibility in Male\nC57BL\/6J Mice","volume":"492","author":"Li","year":"2025","journal-title":"J. Hazard. Mater."},{"issue":"11","key":"2026101607062300800_cit33","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 Purified\nDiets for Laboratory Rodents: Final Report of the American Institute\nof Nutrition Ad Hoc Writing Committee on the Reformulation of the\nAIN-76A Rodent Diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"issue":"6","key":"2026101607062300800_cit34","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/nprot.2010.50","article-title":"Global Metabolic Profiling\nProcedures for Urine Using UPLC\u2013MS","volume":"5","author":"Want","year":"2010","journal-title":"Nat.\nProtoc."},{"issue":"3","key":"2026101607062300800_cit35","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1021\/ac051437y","article-title":"XCMS: Processing Mass\nSpectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment,\nMatching, and Identification","volume":"78","author":"Smith","year":"2006","journal-title":"Anal. Chem."},{"issue":"18","key":"2026101607062300800_cit36","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1071\/RD20107","article-title":"Calorie Restriction\nduring Gestation Affects Ovarian Reserve in Offspring in the Mouse","volume":"32","author":"Zanini","year":"2020","journal-title":"Reprod., Fertil. Dev."},{"issue":"1","key":"2026101607062300800_cit37","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13048-017-0372-x","article-title":"Food Restriction\nduring Pregnancy and Female Offspring Fertility: Adverse Effects of\nReprogrammed Reproductive Lifespan","volume":"10","author":"Harrath","year":"2017","journal-title":"J. Ovarian\nRes."},{"issue":"4","key":"2026101607062300800_cit38","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1095\/biolreprod.112.107235","article-title":"Maternal Undernutrition\nin Cows Impairs Ovarian and\nCardiovascular Systems in Their Offspring","volume":"88","author":"Mossa","year":"2013","journal-title":"Biol.\nReprod."},{"issue":"8","key":"2026101607062300800_cit39","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay3047","article-title":"The\nHidden Costs of Dietary Restriction: Implications for Its Evolutionary\nand Mechanistic Origins","volume":"6","author":"McCracken","year":"2020","journal-title":"Sci. Adv."},{"issue":"5","key":"2026101607062300800_cit40","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.jhep.2017.05.023","article-title":"High-Fat Diet Disrupts\nEndoplasmic Reticulum Calcium Homeostasis in the Rat Liver","volume":"67","author":"Wires","year":"2017","journal-title":"J. Hepatol."},{"issue":"1","key":"2026101607062300800_cit41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s12974-024-03107-6","article-title":"Interaction\nof High-Fat\nDiet and Brain Trauma Alters Adipose Tissue Macrophages and Brain\nMicroglia Associated with Exacerbated Cognitive Dysfunction","volume":"21","author":"Henry","year":"2024","journal-title":"J. Neuroinflammation"},{"issue":"8","key":"2026101607062300800_cit42","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.trecan.2021.06.005","article-title":"High-Fat Diet\nImpacts on Tumor Development in the Gut","volume":"7","author":"van Driel","year":"2021","journal-title":"Trends\nCancer"},{"issue":"2","key":"2026101607062300800_cit43","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1093\/toxsci\/kfz003","article-title":"Ozone Exposure during\nImplantation Increases Serum Bioactivity in HTR-8\/SVneo Trophoblasts","volume":"168","author":"Miller","year":"2019","journal-title":"Toxicol. Sci."},{"issue":"11","key":"2026101607062300800_cit44","doi-asserted-by":"publisher","first-page":"117011","DOI":"10.1289\/ehp13217","article-title":"Evaluating the Effect\nof Gestational Exposure to Perfluorohexane Sulfonate on Placental\nDevelopment in Mice Combining Alternative Splicing and Gene Expression\nAnalyses","volume":"131","author":"Zhang","year":"2023","journal-title":"Environ. Health Perspect."},{"key":"2026101607062300800_cit45","doi-asserted-by":"publisher","first-page":"101094","DOI":"10.1016\/j.molmet.2020.101094","article-title":"Ozone-Induced Fetal\nGrowth Restriction in Rats Is Associated with Sexually Dimorphic Placental\nand Fetal Metabolic Adaptation","volume":"42","author":"Miller","year":"2020","journal-title":"Mol. Metab."},{"issue":"12","key":"2026101607062300800_cit46","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202201514r","article-title":"Prenatal\nOzone Exposure Programs a Sexually Dimorphic\nSusceptibility to High-Fat Diet in Adolescent Long-Evans Rats","volume":"36","author":"Stewart","year":"2022","journal-title":"FASEB J."},{"issue":"35","key":"2026101607062300800_cit47","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305472","article-title":"Maternal High-Fat Diet in Lactation Impacts\nHypothalamic Neurogenesis and Neurotrophic Development, Leading to\nLater Life Susceptibility to Obesity in Male but Not Female Mice","volume":"10","author":"Xu","year":"2023","journal-title":"Adv. Sci."}],"container-title":["Environment &amp; Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/envhealth.5c00865","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ehnea2\/article-pdf\/4\/10\/2219\/66263441\/envhealth.5c00865.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ehnea2\/article-pdf\/4\/10\/2219\/66263441\/envhealth.5c00865.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:13:49Z","timestamp":1792149229000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ehnea2\/article\/4\/10\/2219\/5232965\/Dietary-Patterns-Modulate-Ozone-Induced"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,6,2]]},"published-print":{"date-parts":[[2026,10,16]]}},"URL":"https:\/\/doi.org\/10.1021\/envhealth.5c00865","relation":{},"ISSN":["2833-8278"],"issn-type":[{"value":"2833-8278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]}}}