{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:13:26Z","timestamp":1790345606709,"version":"4.1.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"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":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Zearalenone (ZEN), a mycotoxin from <jats:italic>Fusarium<\/jats:italic> species, is widely present in contaminated grains and animal products. It exerts estrogen-like effects, disrupting hormonal balance and reproductive function, partly through oxidative stress-induced DNA damage. The ATM-Chk2-p53 pathway is a key mediator of the DNA damage response. Melatonin (MT), a natural antioxidant, supports ovarian function by regulating hormone secretion and reducing oxidative stress. This study explores whether MT alleviates ZEN-induced ovarian and granulosa cell damage via the ATM-Chk2-p53 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female mice were exposed to ZEN (0.8mg\/kg) with or without MT (10, 20, or 40 mg\/kg) for 28 days. Ovarian morphology, hormone levels, oxidative stress markers, and DNA damage proteins were assessed. GRM02 cells were treated with ZEN (60 \u03bcM) and\/or MT (100 \u03bcM). Apoptosis, cell cycle, oxidative stress, and DNA damage markers were evaluated. ATM-knockout and ATM-activated GRM02 models were used to examine pathway involvement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ZEN caused ovarian atrophy, estrous disruption, reduced E2, FSH, and LH, elevated oxidative stress, and increased \u03b3H2AX, pATM, Chk2, and p53 expression. MT restored ovarian function, improved antioxidant capacity, and reduced DNA damage. In GRM02 cells, MT mitigated ZEN-induced G2\/M arrest, apoptosis, and oxidative stress. ATM activation enhanced MT\u2019s protective effect, while ATM knockout worsened ZEN toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>MT protects against ZEN-induced ovarian and cellular damage by reducing oxidative stress and modulating the ATM-Chk2-p53 pathway. These findings highlight MT\u2019s potential as a protective feed additive against mycotoxin-related reproductive toxicity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2025.1587391","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:57:08Z","timestamp":1754917028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Melatonin ameliorates zearalenone-induced ovarian damage in mice through antioxidative effects"],"prefix":"10.3389","volume":"12","author":[{"given":"Yi","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongran","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengli","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1016\/j.csbj.2023.02.048","article-title":"Mechanistic insights into zearalenone-accelerated colorectal cancer in mice using integrative multi-omics approaches","volume":"21","author":"Lo","year":"2023","journal-title":"Comput Struct Biotechnol J"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11100552","article-title":"Zearalenone biodegradation by the combination of probiotics with cell-free extracts of aspergillus oryzae and its mycotoxin-alleviating effect on pig production performance","volume":"11","author":"Liu","year":"2019","journal-title":"Toxins (Basel)"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"629006","DOI":"10.3389\/fvets.2021.629006","article-title":"Dose-effect of zearalenone on the localization and expression of growth hormone, growth hormone receptor, and heat shock protein 70 in the ovaries of post-weaning gilts","volume":"8","author":"Song","year":"2021","journal-title":"Front Vet Sci"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252011003","article-title":"Protective and detoxifying effects of resveratrol on zearalenone-mediated toxicity: a review","volume":"25","author":"Lv","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30030505","article-title":"Reproductive toxicity of zearalenone and its molecular mechanisms: a review","volume":"30","author":"Lv","year":"2025","journal-title":"Molecules"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"114710","DOI":"10.1016\/j.ecoenv.2023.114710","article-title":"Zearalenone induces mitochondria-associated endoplasmic reticulum membranes dysfunction in piglet sertoli cells based on endoplasmic reticulum stress","volume":"254","author":"Ma","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010217","article-title":"Kaempferol inhibits zearalenone-induced oxidative stress and apoptosis via the PI3K\/AKT-mediated NRF2 signaling pathway: in vitro and in vivo studies","volume":"22","author":"Rajendran","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"6763","DOI":"10.1007\/s00018-021-03926-3","article-title":"DNA damage responses that enhance resilience to replication stress","volume":"78","author":"Yoshida","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.1091\/mbc.e16-01-0032","article-title":"Hyperactivation of atm upon DNA-pkcs inhibition modulates p53 dynamics and cell fate in response to DNA damage","volume":"27","author":"Finzel","year":"2016","journal-title":"Mol Biol Cell"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12915-021-00965-x","article-title":"Sustained chk 2 activity, but not atm activity, is critical to maintain a g1 arrest after DNA damage in untransformed cells","volume":"19","author":"Garcia-Santisteban","year":"2021","journal-title":"BMC Biol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"103269","DOI":"10.1016\/j.redox.2024.103269","article-title":"Oxidative stress and the multifaceted roles of atm in maintaining cellular redox homeostasis","volume":"75","author":"Lee","year":"2024","journal-title":"Redox Biol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"101511","DOI":"10.1016\/j.redox.2020.101511","article-title":"Mitochondria at the crossroads of atm-mediated stress signaling and regulation of reactive oxygen species","volume":"32","author":"Lee","year":"2020","journal-title":"Redox Biol"},{"key":"ref13","first-page":"461","article-title":"The role of autoimmunity in premature ovarian failure","volume":"13","author":"Ebrahimi","year":"2015","journal-title":"Iran J Reprod Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13048-015-0162-2","article-title":"Micrornas in ovarian function and disorders","volume":"8","author":"Li","year":"2015","journal-title":"J Ovarian Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"114007","DOI":"10.1016\/j.envpol.2020.114007","article-title":"Whole-transcriptome analysis of the toxic effects of zearalenone exposure on cerna networks in porcine granulosa cells","volume":"261","author":"Li","year":"2020","journal-title":"Environ Pollut"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1508-2","article-title":"Small extracellular vesicles derived from embryonic stem cells restore ovarian function of premature ovarian failure through PI3K\/AKT signaling pathway","volume":"11","author":"Liu","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1530\/REP-16-0641","article-title":"Melatonin levels in follicular fluid as markers for ivf outcomes and predicting ovarian reserve","volume":"153","author":"Tong","year":"2017","journal-title":"Reproduction"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1080\/09513590.2017.1409713","article-title":"Melatonin concentration in follicular fluid is correlated with antral follicle count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive technology (ART) procedures","volume":"34","author":"Zheng","year":"2018","journal-title":"Gynecol Endocrinol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1007\/s11010-021-04151-z","article-title":"Melatonin and its mechanism of action in the female reproductive system and related malignancies","volume":"476","author":"Ezzati","year":"2021","journal-title":"Mol Cell Biochem"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"35165","DOI":"10.1038\/srep35165","article-title":"Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice","volume":"6","author":"Song","year":"2016","journal-title":"Sci Rep"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.fertnstert.2014.06.014","article-title":"Melatonin and the circadian system: contributions to successful female reproduction","volume":"102","author":"Reiter","year":"2014","journal-title":"Fertil Steril"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031135","article-title":"Importance of melatonin in assisted reproductive technology and ovarian aging","volume":"21","author":"Tamura","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1111\/j.1600-079X.2007.00524.x","article-title":"Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate","volume":"44","author":"Tamura","year":"2008","journal-title":"J Pineal Res"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"7718155","DOI":"10.1155\/2023\/7718155","article-title":"Melatonin repairs osteoporotic bone defects in iron-overloaded rats through pi3k\/akt\/gsk-3beta\/p70s6k signaling pathway","volume":"2023","author":"Ren","year":"2023","journal-title":"Oxidative Med Cell Longev"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e0154427","DOI":"10.1371\/journal.pone.0154427","article-title":"Melatonin preserves blood-brain barrier integrity and permeability via matrix metalloproteinase-9 inhibition","volume":"11","author":"Alluri","year":"2016","journal-title":"PLoS One"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1093\/jas\/skaa372","article-title":"Supplementing merino ewes with melatonin during the last half of pregnancy improves tolerance of prolonged parturition and survival of second-born twin lambs","volume":"98","author":"Flinn","year":"2020","journal-title":"J Anim Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1177\/0192623315570339","article-title":"Vaginal cytology of the laboratory rat and mouse: review and criteria for the staging of the estrous cycle using stained vaginal smears","volume":"43","author":"Cora","year":"2015","journal-title":"Toxicol Pathol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e15558","DOI":"10.1371\/journal.pone.0015558","article-title":"Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring","volume":"5","author":"Bernal","year":"2010","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10071045","article-title":"Melatonin ameliorates the toxicity induced by deoxynivalenol in murine ovary granulosa cells by antioxidative and anti-inflammatory effects","volume":"10","author":"Fan","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24132474","article-title":"Treatment with, resveratrol, a sirt 1 activator, prevents zearalenone-induced lactic acid metabolism disorder in rat sertoli cells","volume":"24","author":"Cai","year":"2019","journal-title":"Molecules"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.theriogenology.2019.06.008","article-title":"Melatonin treatment and male replacement every week on the reproductive performance in sarda sheep breed","volume":"135","author":"Mura","year":"2019","journal-title":"Theriogenology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"3297","DOI":"10.3390\/toxins7083297","article-title":"Zearalenone and its derivatives alpha-zearalenol and beta-zearalenol decontamination by Saccharomyces cerevisiae strains isolated from bovine forage","volume":"7","author":"Keller","year":"2015","journal-title":"Toxins (Basel)"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14100653","article-title":"Effects of zearalenone on production performance, egg quality, ovarian function and gut microbiota of laying hens","volume":"14","author":"Yuan","year":"2022","journal-title":"Toxins (Basel)"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.mce.2017.08.010","article-title":"Zearalenone and alpha-zearalenol inhibit the synthesis and secretion of pig follicle stimulating hormone via the non-classical estrogen membrane receptor gpr 30","volume":"461","author":"He","year":"2018","journal-title":"Mol Cell Endocrinol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3389\/fgene.2018.00667","article-title":"Zearalenone: a mycotoxin with different toxic effect in domestic and laboratory animals' granulosa cells","volume":"9","author":"Zhang","year":"2018","journal-title":"Front Genet"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.3390\/toxins16120509","article-title":"The potential influence of the presence of mycotoxins in human follicular fluid on reproductive outcomes","volume":"16","author":"Szentirmay","year":"2024","journal-title":"Toxins (Basel)"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"434","DOI":"10.2174\/1570159X14666161228122115","article-title":"Melatonin: pharmacology, functions and therapeutic benefits","volume":"15","author":"Tordjman","year":"2017","journal-title":"Curr Neuropharmacol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"140","DOI":"10.2741\/875","article-title":"Modulation of human ovarian function by melatonin","volume":"13","author":"Rai","year":"2021","journal-title":"Front Biosci (Elite Ed)"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/rda.13378","article-title":"Effects of melatonin on oocyte developmental competence and the role of melatonin receptor 1 in juvenile goats","volume":"54","author":"Soto-Heras","year":"2019","journal-title":"Reprod Domest Anim"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"759","DOI":"10.5664\/jcsm.10424","article-title":"Management of rem sleep behavior disorder: an american academy of sleep medicine clinical practice guideline","volume":"19","author":"Howell","year":"2023","journal-title":"J Clin Sleep Med"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"129","DOI":"10.5664\/jcsm.5412","article-title":"The evolution of the aasm clinical practice guidelines: another step forward","volume":"12","author":"Morgenthaler","year":"2016","journal-title":"J Clin Sleep Med"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1210\/jcem-65-3-407","article-title":"Circulating intact parathyroid hormone measured by a two-site immunochemiluminometric assay","volume":"65","author":"Brown","year":"1987","journal-title":"J Clin Endocrinol Metab"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.3892\/mmr.2019.10014","article-title":"Estrogen receptor beta suppresses inflammation and the progression of prostate cancer","volume":"19","author":"Xiao","year":"2019","journal-title":"Mol Med Rep"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.arr.2018.07.010","article-title":"The role of melatonin, a multitasking molecule, in retarding the processes of ageing","volume":"47","author":"Majidinia","year":"2018","journal-title":"Ageing Res Rev"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1667\/RR13855.1","article-title":"Induction and repair of DNA dsb as revealed by h2ax phosphorylation foci in human fibroblasts exposed to low- and high-let radiation: relationship with early and delayed reproductive cell death","volume":"183","author":"Antonelli","year":"2015","journal-title":"Radiat Res"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"2371173","DOI":"10.1080\/13510002.2024.2371173","article-title":"Navigating the redox landscape: reactive oxygen species in regulation of cell cycle","volume":"29","author":"Mackova","year":"2024","journal-title":"Redox Rep"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"eadi2421","DOI":"10.1126\/science.adi2421","article-title":"Cdk4\/6 activity is required during g(2) arrest to prevent stress-induced endoreplication","volume":"384","author":"Mckenney","year":"2024","journal-title":"Science"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1093\/nar\/gkr596","article-title":"DNA damage bypass operates in the s and g2 phases of the cell cycle and exhibits differential mutagenicity","volume":"40","author":"Diamant","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"981","DOI":"10.7150\/jca.88160","article-title":"Fen1 promotes hepatocellular carcinoma progression by activating cell cycle transition from g2 to m phase","volume":"15","author":"Wang","year":"2024","journal-title":"J Cancer"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/s41580-021-00394-2","article-title":"Cellular functions of the protein kinase ATM and their relevance to human disease","volume":"22","author":"Lee","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"875132","DOI":"10.3389\/fcell.2022.875132","article-title":"Atm modulates nuclear mechanics by regulating Lamin a levels","volume":"10","author":"Shah","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"3738","DOI":"10.1002\/1878-0261.13058","article-title":"Ubqln4 is an atm substrate that stabilizes the anti-apoptotic proteins bcl2a1 and bcl2l10 in mesothelioma","volume":"15","author":"Liu","year":"2021","journal-title":"Mol Oncol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.canlet.2019.02.015","article-title":"Usp39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing chk2","volume":"449","author":"Wu","year":"2019","journal-title":"Cancer Lett"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12943-024-01933-z","article-title":"The DNA damage sensor atm kinase interacts with the p53 mrna and guides the DNA damage response pathway","volume":"23","author":"Karakostis","year":"2024","journal-title":"Mol Cancer"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.tibs.2011.10.002","article-title":"The atm protein kinase and cellular redox signaling: beyond the DNA damage response","volume":"37","author":"Ditch","year":"2012","journal-title":"Trends Biochem Sci"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1126\/science.1192912","article-title":"Atm activation by oxidative stress","volume":"330","author":"Guo","year":"2010","journal-title":"Science"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.dnarep.2014.11.004","article-title":"The complexity of DNA double strand break is a crucial factor for activating atr signaling pathway for g2\/m checkpoint regulation regardless of atm function","volume":"25","author":"Xue","year":"2015","journal-title":"DNA Repair (Amst)"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260698","article-title":"Live-cell tracking of gamma-h2ax kinetics reveals the distinct modes of ATM and DNA-PK in the immediate response to DNA damage","volume":"136","author":"Trakarnphornsombat","year":"2023","journal-title":"J Cell Sci"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s11010-011-1156-z","article-title":"Ionizing radiation induced signaling of DNA damage response molecules in raw 264.7 and cd4(+) t cells","volume":"363","author":"Dhariwala","year":"2012","journal-title":"Mol Cell Biochem"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"e50500","DOI":"10.15252\/embr.202050500","article-title":"Redox activation of atm enhances gsnor translation to sustain mitophagy and tolerance to oxidative stress","volume":"22","author":"Cirotti","year":"2021","journal-title":"EMBO Rep"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.bmcl.2017.01.045","article-title":"Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (atr)","volume":"27","author":"Ramachandran","year":"2017","journal-title":"Bioorg Med Chem Lett"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41392-020-00381-7","article-title":"A disease-relevant mutation of spop highlights functional significance of atm-mediated DNA damage response","volume":"6","author":"Xiao","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1038\/onc.2011.469","article-title":"Melatonin triggers p53ser phosphorylation and prevents DNA damage accumulation","volume":"31","author":"Santoro","year":"2012","journal-title":"Oncogene"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1111\/j.1600-079X.2011.00906.x","article-title":"Nickel exposure induces oxidative damage to mitochondrial DNA in neuro 2a cells: the neuroprotective roles of melatonin","volume":"51","author":"Xu","year":"2011","journal-title":"J Pineal Res"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"102570","DOI":"10.1016\/j.redox.2022.102570","article-title":"Decreased autophagosome biogenesis, reduced Nrf2, and enhanced ferroptotic cell death are underlying molecular mechanisms of non-alcoholic fatty liver disease","volume":"59","author":"Liu","year":"2023","journal-title":"Redox Biol"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.3390\/biom10020320","article-title":"Regulation of Nrf2 by mitochondrial reactive oxygen species in physiology and pathology","volume":"10","author":"Kasai","year":"2020","journal-title":"Biomol Ther"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1017\/erm.2020.3","article-title":"DNA damage checkpoint kinases in cancer","volume":"22","author":"Smith","year":"2020","journal-title":"Expert Rev Mol Med"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41418-021-00845-5","article-title":"A novel cdc25a\/dyrk2 regulatory switch modulates cell cycle and survival","volume":"29","author":"Lara-Chica","year":"2022","journal-title":"Cell Death Differ"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"4676","DOI":"10.1158\/0008-5472.CAN-20-2723","article-title":"Atr\/atm-mediated phosphorylation of brca1 t1394 promotes homologous recombinational repair and g(2)-m checkpoint maintenance","volume":"81","author":"Foo","year":"2021","journal-title":"Cancer Res"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1038\/s12276-021-00659-y","article-title":"Phospholipase d2 is a positive regulator of sirtuin 1 and modulates p53-mediated apoptosis via sirtuin 1","volume":"53","author":"Lee","year":"2021","journal-title":"Exp Mol Med"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"3997","DOI":"10.1073\/pnas.1416031112","article-title":"Atm prevents dsb formation by coordinating ssb repair and cell cycle progression","volume":"112","author":"Khoronenkova","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"2877","DOI":"10.3390\/biom5042877","article-title":"Atm-dependent phosphorylation of all three members of the mrn complex: from sensor to adaptor","volume":"5","author":"Lavin","year":"2015","journal-title":"Biomol Ther"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"2638","DOI":"10.1038\/s41467-022-30303-w","article-title":"Mrnip condensates promote DNA double-strand break sensing and end resection","volume":"13","author":"Wang","year":"2022","journal-title":"Nat Commun"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"110826","DOI":"10.1016\/j.isci.2024.110826","article-title":"Diffusion of activated ATM explains gammaH2AX and MDC1 spread beyond the DNA damage site","volume":"27","author":"Danovski","year":"2024","journal-title":"iScience"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1587391\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:57:09Z","timestamp":1754917029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1587391\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":74,"alternative-id":["10.3389\/fvets.2025.1587391"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2025.1587391","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]},"article-number":"1587391"}}