{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:57:37Z","timestamp":1792727857914,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>Polyethylene microplastics (PE-MPs), now pervasive environmental contaminants, have been implicated in reproductive toxicity, but their mechanistic effects on testicular function remain poorly defined. This study investigates the mechanistic basis of PE-MPs\u2013induced male reproductive toxicity in a rodent model (Wistar rats), with a specific focus on testicular mitochondrial redox homeostasis and oxidative phosphorylation. By integrating mitochondrial bioenergetics, redox signaling, histopathology, and reproductive endpoints, the work advances mechanistic toxicology insights relevant to environmental reproductive health. Fifteen male rats were randomly divided into three groups: control, and PE-MPs treated groups receiving 15 or 60\u00a0mg\/kg body weight orally for 28\u00a0days. Testicular mitochondria were isolated to evaluate activities of tricarboxylic acid (TCA) cycle enzymes, citrate synthase (CS), isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH), as well as respiratory chain complexes I\u2013IV. Mitochondrial redox balance indices, including malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), were also assessed. PE-MP exposure induced a dose-dependent suppression of TCA cycle and electron transport activities, with CS and SDH inhibited by up to 50% at the highest dose suggesting a broad inhibition of electron transport and ATP synthesis. These mitochondrial impairments coincided with elevated MDA and MPO levels, and significant depletion of GSH, CAT, and SOD, indicating profound mitochondrial oxidative distress. These mitochondrial disturbances correlated with histological evidence of testicular degeneration and decreased testosterone levels. Collectively, the findings of this study highlight that PE-MPs compromise testicular bioenergetics and function by disrupting testicular oxidative phosphorylation and redox homeostasis, leading to mitochondrial dysfunction, structural degeneration, and impaired steroidogenesis, providing mechanistic insight into microplastic-induced male infertility. Understanding this bioenergetic collapse provides a biochemical framework for assessing the reproductive toxicity of microplastics and underscores the urgency of mitigating their exposure in vulnerable populations.<\/jats:p>","DOI":"10.3389\/ftox.2026.1699288","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:13:21Z","timestamp":1768454001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Testicular mitochondrial redox imbalance and impaired oxidative phosphorylation underlie microplastic-induced testicular dysfunction in Wistar rats"],"prefix":"10.3389","volume":"8","author":[{"given":"Samuel Abiodun","family":"Kehinde","sequence":"first","affiliation":[{"name":"Biomedical Technology Research Group for Vulnerable Populations and School of Health Science, Mae Fah Luang University","place":["Chiang Rai, Thailand"]},{"name":"Biochemical Toxicology Laboratory, Department of Environmental Health Sciences, Faculty of Basic Medical Sciences, Ajayi Crowther University","place":["Oyo, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolulope Peter","family":"Fatokun","sequence":"additional","affiliation":[{"name":"Department of Drug Toxicology and Safety Pharmacology, Faculty of Life Sciences, University of Bradford","place":["Bradford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarva Mangala","family":"Praveena","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia","place":["Serdang, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abosede Temitope","family":"Olajide","sequence":"additional","affiliation":[{"name":"Cell and Signaling Laboratory, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM)","place":["Serdang, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chau Ling","family":"Tham","sequence":"additional","affiliation":[{"name":"Cell and Signaling Laboratory, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM)","place":["Serdang, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Teles","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasitorn","family":"Chusri","sequence":"additional","affiliation":[{"name":"Biomedical Technology Research Group for Vulnerable Populations and School of Health Science, Mae Fah Luang University","place":["Chiang Rai, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/mrd.22871","article-title":"Reactive oxygen species as mediators of sperm capacitation and pathological damage","volume":"84","author":"Aitken","year":"2017","journal-title":"Mol. Reproduction Dev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"581838","DOI":"10.3389\/fendo.2020.581838","article-title":"The role of genetics and oxidative stress in the etiology of Male Infertility\u2014A unifying hypothesis?","volume":"11","author":"Aitken","year":"2020","journal-title":"Front. Endocrinol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.2164\/jandrol.112.016535","article-title":"Reactive oxygen species and sperm Function\u2014In sickness and in health","volume":"33","author":"Aitken","year":"2012","journal-title":"J. Androl."},{"key":"B4","doi-asserted-by":"publisher","first-page":"134625","DOI":"10.1016\/j.scitotenv.2019.134625","article-title":"Microplastics in wild fish from north east Atlantic Ocean and its potential for causing neurotoxic effects, lipid oxidative damage, and human health risks associated with ingestion exposure","volume":"717","author":"Barboza","year":"2020","journal-title":"Sci. Total Environ."},{"key":"B5","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.taap.2012.04.009","article-title":"Impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity","volume":"261","author":"Bhattacharya","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1093\/humrep\/deg199","article-title":"Evaluation of the one\u2010step eosin\u2010nigrosin staining technique for human sperm vitality assessment","volume":"18","author":"Bj\u00f6rndahl","year":"2003","journal-title":"Hum. Reprod."},{"key":"B7","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem. J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s43591-024-00090-w","article-title":"Quantitation of micro and nanoplastics in human blood by pyrolysis-gas chromatography\u2013mass spectrometry","volume":"4","author":"Brits","year":"2024","journal-title":"Microplastics Nanoplastics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.3390\/ijerph17041212","article-title":"A detailed review study on potential effects of microplastics and additives of concern on human health","volume":"17","author":"Campanale","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1111\/j.1745-7262.2006.00202.x","article-title":"Effects of epidermal growth factor on sperm content and motility of rats with surgically induced varicoceles","volume":"8","author":"Cheng","year":"2006","journal-title":"Asian J. Androl."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1111\/gcb.14020","article-title":"Microplastics as an emerging threat to terrestrial ecosystems","volume":"24","author":"de Souza Machado","year":"2018","journal-title":"Glob. Change Biol."},{"key":"B12","first-page":"300","article-title":"Methods for estimating lipid peroxidation: an analysis of merits and demerits","volume":"40","author":"Devasagayam","year":"2003","journal-title":"Indian J. Biochem. and Biophysics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"901798","DOI":"10.3389\/ftox.2022.901798","article-title":"Developmental and reproductive toxic effects of exposure to microplastics: a review of associated signaling pathways","volume":"4","author":"Dubey","year":"2022","journal-title":"Front. Toxicol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e2368","DOI":"10.1002\/bdr2.2368","article-title":"Oral exposure to polystyrene nanoplastics altered the hypothalamic\u2013pituitary\u2013testicular axis role in hormonal regulation, inducing reproductive toxicity in albino rats","volume":"116","author":"Ebrahim","year":"2024","journal-title":"Birth Defects Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/environments10110194","article-title":"The plastic within: microplastics invading human organs and bodily fluids systems","volume":"10","author":"Enyoh","year":"2023","journal-title":"Environments"},{"key":"B16","doi-asserted-by":"publisher","first-page":"153545","DOI":"10.1016\/j.tox.2023.153545","article-title":"Hematological consequences of polyethylene microplastics toxicity in Male rats: oxidative stress, genetic, and epigenetic links","volume":"492","author":"Farag","year":"2023","journal-title":"Toxicology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.mito.2009.12.148","article-title":"Isolation of mitochondria for biogenetical studies: an update","volume":"10","author":"Fern\u00e1ndez-Vizarra","year":"2010","journal-title":"Mitochondrion"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1038\/oby.2011.166","article-title":"Role of skeletal muscle mitochondrial density on exercise\u2010stimulated lipid oxidation","volume":"20","author":"Galgani","year":"2012","journal-title":"Obesity"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1101\/2023.06.02.542598","article-title":"In vivo tissue distribution of microplastics and systemic metabolomic alterations after gastrointestinal exposure","author":"Garcia","year":"2023","journal-title":"bioRxiv"},{"key":"B20","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/s0021-9258(18)57021-6","article-title":"Determination of serum proteins by means of the biuret reaction","volume":"177","author":"Gornall","year":"1949","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0009-8981(98)00060-6","article-title":"Determination of nitrite\/nitrate in human biological material by the simple griess reaction","volume":"274","author":"Guevara","year":"1998","journal-title":"Clin. Chim. Acta"},{"key":"B40","article-title":"Institute of laboratory animal resources (U.S.). Committee on care and use of laboratory animals. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, 1986","year":"2010"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12858-018-0097-5","article-title":"Simple spectrophotometric assay for measuring catalase activity in biological tissues","volume":"19","author":"Hadwan","year":"2018","journal-title":"BMC Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e4758","DOI":"10.21769\/BioProtoc.4758","article-title":"Measuring myeloperoxidase activity as a marker of inflammation in gut tissue samples of mice and rat","volume":"13","author":"Hanning","year":"2023","journal-title":"Bio-protocol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"175825","DOI":"10.1016\/j.scitotenv.2024.175825","article-title":"Assessment of microplastics in human stool: a pilot study investigating the potential impact of diet-associated scenarios on oral microplastics exposure","volume":"951","author":"Hartmann","year":"2024","journal-title":"Sci. Total Environ."},{"key":"B25","doi-asserted-by":"publisher","first-page":"897029","DOI":"10.3389\/fendo.2022.897029","article-title":"Mechanism of inflammatory associated impairment of sperm function, spermatogenesis and steroidogenesis","volume":"13","author":"Hasan","year":"2022","journal-title":"Front. Endocrinology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"124028","DOI":"10.1016\/j.jhazmat.2020.124028","article-title":"Reproductive toxicity of polystyrene microplastics: in vivo experimental study on testicular toxicity in mice","volume":"405","author":"Hou","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"B27","doi-asserted-by":"publisher","first-page":"123430","DOI":"10.1016\/j.jhazmat.2020.123430","article-title":"Polystyrene microplastics induced Male reproductive toxicity in mice","volume":"401","author":"Jin","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1159\/000178170","article-title":"Testicular biopsy score Count\u2013A method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males","volume":"1","author":"Johnsen","year":"1970","journal-title":"Hormone Res. Paediatr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ab.2013.07.018","article-title":"A spectrophotometric coupled enzyme assay to measure the activity of succinate dehydrogenase","volume":"442","author":"Jones","year":"2013","journal-title":"Anal. Biochem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"23664","DOI":"10.1038\/s41598-024-74637-5","article-title":"Impact of polyethylene microplastics exposure on kallikrein-3 levels, steroidal-thyroidal hormones, and antioxidant status in murine model: protective potentials of naringin","volume":"14","author":"Kehinde","year":"2024","journal-title":"Sci. Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"41120","DOI":"10.1038\/s41598-025-24887-8","article-title":"Polyethylene microplastics disrupt renal function, mitochondrial bioenergetics, redox homeostasis, and histoarchitecture in wistar rats","volume":"15","author":"Kehinde","year":"2025","journal-title":"Sci. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"30419","DOI":"10.1038\/s41598-024-81931-9","article-title":"Microplastic particles in human blood and their association with coagulation markers","volume":"14","author":"Lee","year":"2024","journal-title":"Sci. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"47921","DOI":"10.1007\/s11356-021-13911-9","article-title":"Polystyrene microplastics induce blood\u2013testis barrier disruption regulated by the MAPK-Nrf2 signaling pathway in rats","volume":"28","author":"Li","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.mycres.2009.02.012","article-title":"Cloning, expression and biochemical characterization of mitochondrial and cytosolic malate dehydrogenase from Phytophthora infestans","volume":"113","author":"L\u00f3pez-Calcagno","year":"2009","journal-title":"Mycol. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"113970","DOI":"10.1016\/j.fct.2023.113970","article-title":"Microplastics cause reproductive toxicity in Male mice through inducing apoptosis of spermatogenic cells via p53 signaling","volume":"179","author":"Lu","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.mito.2009.05.001","article-title":"Development and implementation of standardized respiratory chain spectrophotometric assays for clinical diagnosis","volume":"9","author":"Medja","year":"2009","journal-title":"Mitochondrion"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","article-title":"The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase","volume":"247","author":"Misra","year":"1972","journal-title":"J. Biol. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/0304-4165(79)90289-7","article-title":"Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver","volume":"582","author":"Moron","year":"1979","journal-title":"Biochimica Biophysica Acta"},{"key":"B39","doi-asserted-by":"publisher","first-page":"539","DOI":"10.3390\/genes15050539","article-title":"Oxidative stress biomarkers in Male infertility: established methodologies and future perspectives","volume":"15","author":"Mottola","year":"2024","journal-title":"Genes."},{"key":"B41","doi-asserted-by":"publisher","first-page":"23357","DOI":"10.1074\/jbc.M100320200","article-title":"Modulation of mitochondrial function by hydrogen peroxide","volume":"276","author":"Nulton-Persson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15376516.2025.2510525","article-title":"Implications of plastic-derived endocrine disruptors on human health","volume":"35","author":"Ojo","year":"2025","journal-title":"Toxicol. Mech. Methods"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e13669","DOI":"10.1111\/and.13669","article-title":"Selenium attenuates diclofenac\u2010induced testicular and epididymal toxicity in rats","volume":"52","author":"Owumi","year":"2020","journal-title":"Andrologia"},{"key":"B44","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.toxlet.2020.01.008","article-title":"Repeated-oral dose toxicity of polyethylene microplastics and the possible implications on reproduction and development of the next generation","volume":"324","author":"Park","year":"2020","journal-title":"Toxicol. Letters"},{"key":"B45","doi-asserted-by":"publisher","first-page":"8023","DOI":"10.1038\/s41467-023-43788-w","article-title":"Microplastic burden in marine benthic invertebrates depends on species traits and feeding ecology within biogeographical provinces","volume":"14","author":"Porter","year":"2023","journal-title":"Nat. Commun."},{"key":"B46","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s43591-025-00129-6","article-title":"Microplastics in human feces: a pilot study exploring links with dietary habits","volume":"5","author":"Refosco","year":"2025","journal-title":"Microplastics Nanoplastics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e0176056","DOI":"10.1371\/journal.pone.0176056","article-title":"Biochemical and molecular characterization of the isocitrate dehydrogenase with dual coenzyme specificity from the obligate methylotroph Methylobacillus flagellatus","volume":"12","author":"Romkina","year":"2017","journal-title":"PLoS ONE"},{"key":"B48","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ab.2010.06.007","article-title":"A new colorimetric assay for glutathione transferase-catalyzed halogen ion release for high-throughput screening","volume":"405","author":"Skopelitou","year":"2010","journal-title":"Anal. Biochem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.jsbmb.2008.03.004","article-title":"Hormonal regulation of spermatogenesis and spermiogenesis","volume":"109","author":"Sofikitis","year":"2008","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.3390\/ani13071132","article-title":"Impact of microplastics and nanoplastics on livestock health: an emerging risk for reproductive efficiency","volume":"13","author":"Urli","year":"2023","journal-title":"Animals"},{"key":"B51","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s11783-025-1999-2","article-title":"Recent advances in microplastics research: impacts on Mammalian sperm and reproductive health","volume":"19","author":"Wang","year":"2025","journal-title":"Front. Environ. Sci. and Eng."},{"key":"B52","first-page":"9","volume-title":"WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction","year":"1999"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.3390\/ijerph17051509","article-title":"Toxicity of microplastics and nanoplastics in Mammalian systems","volume":"17","author":"Yong","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B54","doi-asserted-by":"publisher","first-page":"103545","DOI":"10.1016\/j.micron.2023.103545","article-title":"Effect of nano-selenium on exosomes secretion associated with sperm maturation within the epididymis","volume":"175","author":"Zhou","year":"2023","journal-title":"Micron"}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1699288\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:13:23Z","timestamp":1768454003000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1699288\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":54,"alternative-id":["10.3389\/ftox.2026.1699288"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2026.1699288","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]},"article-number":"1699288"}}