{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:06:52Z","timestamp":1773929212909,"version":"3.50.1"},"reference-count":117,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100006710","name":"Wayne State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007919","name":"University of Massachusetts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007919","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008975","name":"University of Massachusetts Amherst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008975","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["fertstertscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["F&amp;S Science"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.xfss.2025.10.001","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:25Z","timestamp":1760143105000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Environmental factors accelerate epigenetic aging of sperm via mechanistic target of rapamycin\/blood-testis barrier mechanism"],"prefix":"10.1016","volume":"7","author":[{"given":"Olatunbosun","family":"Arowolo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oladele A.","family":"Oluwayiose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg","family":"Sergeyev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Houle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Richard","family":"Pilsner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-5897","authenticated-orcid":false,"given":"Alexander","family":"Suvorov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.xfss.2025.10.001_bib1","doi-asserted-by":"crossref","DOI":"10.1093\/pnasnexus\/pgac040","article-title":"Paternal diet induces transgenerational epigenetic inheritance of DNA methylation signatures and phenotypes in sheep model","volume":"1","author":"Braz","year":"2022","journal-title":"PNAS Nexus"},{"key":"10.1016\/j.xfss.2025.10.001_bib2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/andr.12911","article-title":"Sperm DNA methylation changes after short-term nut supplementation in healthy men consuming a Western-style diet","volume":"9","author":"Salas-Huetos","year":"2021","journal-title":"Andrology"},{"key":"10.1016\/j.xfss.2025.10.001_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms23010001","article-title":"Paternal exercise improves the metabolic health of offspring via epigenetic modulation of the germline","volume":"23","author":"Costa-J\u00fanior","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.xfss.2025.10.001_bib4","doi-asserted-by":"crossref","first-page":"491","DOI":"10.4103\/1673-5374.245473","article-title":"Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring","volume":"14","author":"Spindler","year":"2019","journal-title":"Neural Regen Res"},{"key":"10.1016\/j.xfss.2025.10.001_bib5","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1111\/j.1530-0277.2009.00993.x","article-title":"Effect of alcohol consumption on CpG methylation in the differentially methylated regions of H19 and IG-DMR in male gametes: implications for fetal alcohol spectrum disorders","volume":"33","author":"Ouko","year":"2009","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1016\/j.xfss.2025.10.001_bib6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41421-021-00343-5","article-title":"Sperm epigenetic alterations contribute to inter- and transgenerational effects of paternal exposure to long-term psychological stress via evading offspring embryonic reprogramming","volume":"7","author":"Zheng","year":"2021","journal-title":"Cell Discov"},{"key":"10.1016\/j.xfss.2025.10.001_bib7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jpsychires.2019.06.001","article-title":"PTSD Initiative. DNA methylation from germline cells in veterans with PTSD","volume":"116","author":"Mehta","year":"2019","journal-title":"J Psychiatr Res"},{"key":"10.1016\/j.xfss.2025.10.001_bib8","first-page":"1257","article-title":"Age-related methylation changes in the human sperm epigenome","volume":"15","author":"Bernhardt","year":"2023","journal-title":"Aging"},{"key":"10.1016\/j.xfss.2025.10.001_bib9","doi-asserted-by":"crossref","first-page":"4928","DOI":"10.3390\/jcm12154928","article-title":"Paternal age matters: association with sperm criteria\u2019s- spermatozoa DNA integrity and methylation profile","volume":"12","author":"Lahimer","year":"2023","journal-title":"J Clin Med"},{"key":"10.1016\/j.xfss.2025.10.001_bib10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13072-022-00437-8","article-title":"Effects of paternal exposure to cigarette smoke on sperm DNA methylation and long-term metabolic syndrome in offspring","volume":"15","author":"Liu","year":"2022","journal-title":"Epigenetics Chromatin"},{"key":"10.1016\/j.xfss.2025.10.001_bib11","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1111\/andr.12416","article-title":"Cigarette smoking significantly alters sperm DNA methylation patterns","volume":"5","author":"Jenkins","year":"2017","journal-title":"Andrology"},{"key":"10.1016\/j.xfss.2025.10.001_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2022.118994","article-title":"Semen quality and sperm DNA methylation in relation to long-term exposure to air pollution in fertile men: a cross-sectional study","volume":"300","author":"Cheng","year":"2022","journal-title":"Environ Pollut"},{"key":"10.1016\/j.xfss.2025.10.001_bib13","doi-asserted-by":"crossref","DOI":"10.1093\/eep\/dvae003","article-title":"Exposure to air pollution is associated with DNA methylation changes in sperm","volume":"10","author":"Schrott","year":"2024","journal-title":"Environ Epigenet"},{"key":"10.1016\/j.xfss.2025.10.001_bib14","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.reprotox.2017.10.009","article-title":"Perinatal exposure to low dose 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) alters sperm DNA methylation in adult rats","volume":"75","author":"Suvorov","year":"2018","journal-title":"Reprod Toxicol"},{"key":"10.1016\/j.xfss.2025.10.001_bib15","doi-asserted-by":"crossref","DOI":"10.1093\/eep\/dvx003","article-title":"Human exposure to flame-retardants is associated with aberrant DNA methylation at imprinted genes in sperm","volume":"3","author":"Soubry","year":"2017","journal-title":"Environ Epigenet"},{"key":"10.1016\/j.xfss.2025.10.001_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2024.108577","article-title":"Mixtures of per- and polyfluoroalkyl substances (PFAS) alter sperm methylation and long-term reprogramming of offspring liver and fat transcriptome","volume":"186","author":"Maxwell","year":"2024","journal-title":"Environ Int"},{"key":"10.1016\/j.xfss.2025.10.001_bib17","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/mp.2014.84","article-title":"Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression","volume":"20","author":"Milekic","year":"2015","journal-title":"Mol Psychiatry"},{"key":"10.1016\/j.xfss.2025.10.001_bib18","doi-asserted-by":"crossref","first-page":"E2348","DOI":"10.1073\/pnas.1707337115","article-title":"Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice","volume":"115","author":"Xie","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.xfss.2025.10.001_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.envint.2021.106693","article-title":"Paternal preconception phthalate exposure alters sperm methylome and embryonic programming","volume":"155","author":"Oluwayiose","year":"2021","journal-title":"Environ Int"},{"key":"10.1016\/j.xfss.2025.10.001_bib20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biocel.2015.04.014","article-title":"Germline-derived DNA methylation and early embryo epigenetic reprogramming: the selected survival of imprints","volume":"67","author":"Monk","year":"2015","journal-title":"Int J Biochem Cell Biol"},{"key":"10.1016\/j.xfss.2025.10.001_bib21","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13178","article-title":"The inherited methylome landscape is directly altered with paternal aging and associated with offspring neurodevelopmental disorders","volume":"19","author":"Denomme","year":"2020","journal-title":"Aging Cell"},{"key":"10.1016\/j.xfss.2025.10.001_bib22","first-page":"4996","article-title":"Paternal age effects on sperm FOXK1 and KCNA7 methylation and transmission into the next generation","volume":"25","author":"Atsem","year":"2016","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.xfss.2025.10.001_bib23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/humupd\/dmac033","article-title":"Age-associated epigenetic changes in mammalian sperm: implications for offspring health and development","volume":"29","author":"Ashapkin","year":"2022","journal-title":"Hum Reprod Update"},{"key":"10.1016\/j.xfss.2025.10.001_bib24","author":"Arowolo"},{"key":"10.1016\/j.xfss.2025.10.001_bib25","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1073\/pnas.1321195111","article-title":"Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals","volume":"111","author":"Wei","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.xfss.2025.10.001_bib26","doi-asserted-by":"crossref","DOI":"10.1126\/science.1255903","article-title":"In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism","volume":"345","author":"Radford","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.xfss.2025.10.001_bib27","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.90992","article-title":"Mechanistic target of rapamycin (mTOR) pathway in Sertoli cells regulates age-dependent changes in sperm DNA methylation","volume":"13","author":"Amir","year":"2024","journal-title":"Elife"},{"key":"10.1016\/j.xfss.2025.10.001_bib28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2217\/epi-2020-0404","article-title":"Aging-induced changes in sperm DNA methylation are modified by low dose of perinatal flame retardants","volume":"13","author":"Pilsner","year":"2021","journal-title":"Epigenomics"},{"key":"10.1016\/j.xfss.2025.10.001_bib29","first-page":"1581","article-title":"Sperm epigenetic clock associates with pregnancy outcomes in the general population","volume":"37","author":"Pilsner","year":"2022","journal-title":"Hum Reprod"},{"key":"10.1016\/j.xfss.2025.10.001_bib30","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41398-018-0252-1","article-title":"Exposure to childhood abuse is associated with human sperm DNA methylation","volume":"8","author":"Roberts","year":"2018","journal-title":"Transl Psychiatry"},{"key":"10.1016\/j.xfss.2025.10.001_bib31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.cmet.2015.11.004","article-title":"Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans","volume":"23","author":"Donkin","year":"2016","journal-title":"Cell Metab"},{"key":"10.1016\/j.xfss.2025.10.001_bib32","doi-asserted-by":"crossref","first-page":"E291","DOI":"10.1152\/ajpendo.00038.2020","article-title":"Frequent and mild scrotal heat stress in mice epigenetically alters glucose metabolism in the male offspring","volume":"319","author":"Wan","year":"2020","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10.1016\/j.xfss.2025.10.001_bib33","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1093\/humrep\/dex283","article-title":"Preconception urinary phthalate concentrations and sperm DNA methylation profiles among men undergoing IVF treatment: a cross-sectional study","volume":"32","author":"Wu","year":"2017","journal-title":"Hum Reprod"},{"key":"10.1016\/j.xfss.2025.10.001_bib34","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1093\/toxsci\/kfab002","article-title":"Chronic exposure to cadmium induces differential methylation in mice spermatozoa","volume":"180","author":"Saintilnord","year":"2021","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.xfss.2025.10.001_bib35","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004458","article-title":"Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility","volume":"10","author":"Jenkins","year":"2014","journal-title":"PLoS Genet"},{"key":"10.1016\/j.xfss.2025.10.001_bib36","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13242","article-title":"A germ cell-specific ageing pattern in otherwise healthy men","volume":"19","author":"Laurentino","year":"2020","journal-title":"Aging Cell"},{"key":"10.1016\/j.xfss.2025.10.001_bib37","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s13148-020-00988-1","article-title":"High-resolution analyses of human sperm dynamic methylome reveal thousands of novel age-related epigenetic alterations","volume":"12","author":"Cao","year":"2020","journal-title":"Clin Epigenetics"},{"key":"10.1016\/j.xfss.2025.10.001_bib38","first-page":"961","article-title":"Mammalian target of rapamycin complex (mTOR) pathway modulates blood-testis barrier (BTB) function through F-actin organization and gap junction","volume":"31","author":"Li","year":"2016","journal-title":"Histol Histopathol"},{"key":"10.1016\/j.xfss.2025.10.001_bib39","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/B978-0-12-407704-1.00006-3","article-title":"Regulation of blood-testis barrier (BTB) dynamics during spermatogenesis via the \u201cYin\u201d and \u201cYang\u201d effects of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2","volume":"301","author":"Mok","year":"2013","journal-title":"Int Rev Cell Mol Biol"},{"key":"10.1016\/j.xfss.2025.10.001_bib40","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1096\/fj.12-212977","article-title":"Rictor\/mTORC2 regulates blood-testis barrier dynamics via its effects on gap junction communications and actin filament network","volume":"27","author":"Mok","year":"2013","journal-title":"FASEB J"},{"key":"10.1016\/j.xfss.2025.10.001_bib41","first-page":"207","article-title":"Drug transporters, the blood-testis barrier, and spermatogenesis","volume":"208","author":"Su","year":"2011","journal-title":"J Endocrinol"},{"key":"10.1016\/j.xfss.2025.10.001_bib42","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.micpath.2018.06.037","article-title":"Characterization of inter-Sertoli cell tight and gap junctions in the testis of turtle: Protect the developing germ cells from an immune response","volume":"123","author":"Ahmed","year":"2018","journal-title":"Microb Pathog"},{"key":"10.1016\/j.xfss.2025.10.001_bib43","first-page":"263","article-title":"The blood-testis barrier: its biology, regulation, and physiological role in spermatogenesis","volume":"71","author":"Wong","year":"2005"},{"key":"10.1016\/j.xfss.2025.10.001_bib44","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s12576-010-0130-y","article-title":"Heat stress enhances mTOR signaling after resistance exercise in human skeletal muscle","volume":"61","author":"Kakigi","year":"2011","journal-title":"J Physiol Sci"},{"key":"10.1016\/j.xfss.2025.10.001_bib45","doi-asserted-by":"crossref","first-page":"948","DOI":"10.3389\/fphys.2017.00948","article-title":"Response of turkey muscle satellite cells to thermal challenge. II. Transcriptome effects in differentiating cells","volume":"8","author":"Reed","year":"2017","journal-title":"Front Physiol"},{"key":"10.1016\/j.xfss.2025.10.001_bib46","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/apha.12040","article-title":"Heat stress activates the Akt\/mTOR signalling pathway in rat skeletal muscle","volume":"207","author":"Yoshihara","year":"2013","journal-title":"Acta Physiol (Oxf)"},{"key":"10.1016\/j.xfss.2025.10.001_bib47","doi-asserted-by":"crossref","first-page":"438","DOI":"10.2174\/1567201817666200514080811","article-title":"Heat stress and pulsed unfocused ultrasound: the viability of these physical approaches for drug delivery into testicular seminiferous tubules","volume":"17","author":"Li","year":"2020","journal-title":"Curr Drug Deliv"},{"key":"10.1016\/j.xfss.2025.10.001_bib48","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1002\/mrd.23348","article-title":"Whole-body heat exposure causes developmental stage-specific apoptosis of male germ cells","volume":"87","author":"Yoon","year":"2020","journal-title":"Mol Reprod Dev"},{"key":"10.1016\/j.xfss.2025.10.001_bib49","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/j.1365-2605.2010.01089.x","article-title":"Scrotal heat stress causes a transient alteration in tight junctions and induction of TGF-\u03b2 expression","volume":"34","author":"Cai","year":"2011","journal-title":"Int J Androl"},{"key":"10.1016\/j.xfss.2025.10.001_bib50","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/j.tiv.2015.07.009","article-title":"Metabolomic profiles reveal key metabolic changes in heat stress-treated mouse Sertoli cells","volume":"29","author":"Xu","year":"2015","journal-title":"Toxicol In Vitro"},{"key":"10.1016\/j.xfss.2025.10.001_bib51","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/rda.13131","article-title":"Effect of local scrotal heating on the expression of tight junction-associated molecule Occludin in boar testes","volume":"53","author":"Zhang","year":"2018","journal-title":"Reprod Domest Anim"},{"key":"10.1016\/j.xfss.2025.10.001_bib52","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2409790121","article-title":"Subchronic elevation in ambient temperature drives alterations to the sperm epigenome and accelerates early embryonic development in mice","volume":"121","author":"Trigg","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.xfss.2025.10.001_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2024.173813","article-title":"Impact of heat waves on semen quality: a retrospective study in Argentina between 2005 and 2023","volume":"943","author":"Ver\u00f3n","year":"2024","journal-title":"Sci Total Environ"},{"key":"10.1016\/j.xfss.2025.10.001_bib54","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.semcdb.2016.01.003","article-title":"Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?","volume":"59","author":"Li","year":"2016","journal-title":"Semin Cell Dev Biol"},{"key":"10.1016\/j.xfss.2025.10.001_bib55","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/toxsci\/kfae043","article-title":"The blood-testis barrier disruption is a prerequisite for toxicant-Induced peritubular macrophage increases in the testis of peripubertal rats","volume":"200","author":"Fang","year":"2024","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.xfss.2025.10.001_bib56","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/MED.0000000000000155","article-title":"Actin binding proteins in blood-testis barrier function","volume":"22","author":"Li","year":"2015","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"10.1016\/j.xfss.2025.10.001_bib57","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.reprotox.2017.07.021","article-title":"The environment and male reproduction: the effect of cadmium exposure on reproductive function and its implication in fertility","volume":"73","author":"de Angelis","year":"2017","journal-title":"Reprod Toxicol"},{"key":"10.1016\/j.xfss.2025.10.001_bib58","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3389\/fgene.2020.00527","article-title":"Toxicological effects of cadmium on mammalian testis","volume":"11","author":"Zhu","year":"2020","journal-title":"Front Genet"},{"key":"10.1016\/j.xfss.2025.10.001_bib59","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2024.117623","article-title":"Detrimental effects of cadmium on male infertility: a review","volume":"290","author":"Ze\u010devi\u0107","year":"2025","journal-title":"Ecotoxicol Environ Saf"},{"key":"10.1016\/j.xfss.2025.10.001_bib60","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.molcel.2012.10.016","article-title":"Genome-wide methylation profiles reveal quantitative views of human aging rates","volume":"49","author":"Hannum","year":"2013","journal-title":"Mol Cell"},{"key":"10.1016\/j.xfss.2025.10.001_bib61","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"Horvath","year":"2013","journal-title":"Genome Biol"},{"key":"10.1016\/j.xfss.2025.10.001_bib62","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA methylation-based biomarkers and the epigenetic clock theory of ageing","volume":"19","author":"Horvath","year":"2018","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.xfss.2025.10.001_bib63","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s13059-019-1824-y","article-title":"DNA methylation aging clocks: challenges and recommendations","volume":"20","author":"Bell","year":"2019","journal-title":"Genome Biol"},{"key":"10.1016\/j.xfss.2025.10.001_bib64","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/s43587-023-00462-6","article-title":"Universal DNA methylation age across mammalian tissues","volume":"3","author":"Lu","year":"2023","journal-title":"Nat Aging"},{"key":"10.1016\/j.xfss.2025.10.001_bib65","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21218252","article-title":"Aging induces profound changes in sncRNA in rat sperm and these changes are modified by perinatal exposure to environmental flame retardant","volume":"21","author":"Suvorov","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.xfss.2025.10.001_bib66","doi-asserted-by":"crossref","first-page":"548","DOI":"10.3389\/fendo.2018.00548","article-title":"Developmental exposure to 2,2',4,4'-tetrabromodiphenyl ether permanently alters blood-liver balance of lipids in male mice","volume":"9","author":"Khalil","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"10.1016\/j.xfss.2025.10.001_bib67","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3390\/toxics6020021","article-title":"Transcriptomic analysis of gonadal adipose tissue in male mice exposed perinatally to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)","volume":"6","author":"Abrha","year":"2018","journal-title":"Toxics"},{"key":"10.1016\/j.xfss.2025.10.001_bib68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12940-015-0051-6","article-title":"Endocrine disruptors alter social behaviors and indirectly influence social hierarchies via changes in body weight","volume":"14","author":"Kim","year":"2015","journal-title":"Environ Health"},{"key":"10.1016\/j.xfss.2025.10.001_bib69","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1530\/JME-11-0054","article-title":"Chronic heat stress up-regulates leptin and adiponectin secretion and expression and improves leptin, adiponectin and insulin sensitivity in mice","volume":"48","author":"Morera","year":"2012","journal-title":"J Mol Endocrinol"},{"key":"10.1016\/j.xfss.2025.10.001_bib70","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1175\/1520-0450(2001)040<0762:OTDOAH>2.0.CO;2","article-title":"On the definition of a heat wave","volume":"40","author":"Robinson","year":"2001","journal-title":"J Appl Meteorol Climatol"},{"key":"10.1016\/j.xfss.2025.10.001_bib71","first-page":"173","article-title":"Methods to produce hyperthermia-induced brain dysfunction [Internet]","volume":"162","author":"Sharma","year":"2007"},{"key":"10.1016\/j.xfss.2025.10.001_bib72","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.mehy.2005.12.048","article-title":"Pathophysiological factors underlying heatstroke","volume":"67","author":"Yan","year":"2006","journal-title":"Med Hypotheses"},{"key":"10.1016\/j.xfss.2025.10.001_bib73","doi-asserted-by":"crossref","first-page":"R197","DOI":"10.1152\/ajpregu.00046.2004","article-title":"Heat stress induces a biphasic thermoregulatory response in mice","volume":"288","author":"Leon","year":"2005","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"10.1016\/j.xfss.2025.10.001_bib74","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2144\/000114280","article-title":"Rapid method for the isolation of mammalian sperm DNA","volume":"58","author":"Wu","year":"2015","journal-title":"Biotechniques"},{"key":"10.1016\/j.xfss.2025.10.001_bib75","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1093\/bioinformatics\/btw285","article-title":"RCP: a novel probe design bias correction method for Illumina Methylation BeadChip","volume":"32","author":"Niu","year":"2016","journal-title":"Bioinformatics"},{"key":"10.1016\/j.xfss.2025.10.001_bib76","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The sva package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics"},{"key":"10.1016\/j.xfss.2025.10.001_bib77","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1186\/1471-2105-11-587","article-title":"Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis","volume":"11","author":"Du","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.xfss.2025.10.001_bib78","doi-asserted-by":"crossref","first-page":"4820","DOI":"10.1093\/bioinformatics\/btac583","article-title":"Aclust2.0: a revamped unsupervised R tool for Infinium methylation beadchips data analyses","volume":"38","author":"Oluwayiose","year":"2022","journal-title":"Bioinformatics"},{"issue":"Suppl 2","key":"10.1016\/j.xfss.2025.10.001_bib79","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1186\/1753-6561-6-S2-S10","article-title":"Genomic selection using regularized linear regression models: ridge regression, lasso, elastic net and their extensions","volume":"6","author":"Ogutu","year":"2012","journal-title":"BMC Proc"},{"key":"10.1016\/j.xfss.2025.10.001_bib80","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"},{"key":"10.1016\/j.xfss.2025.10.001_bib81","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.xfss.2025.10.001_bib82","doi-asserted-by":"crossref","DOI":"10.34172\/jlms.2024.43","article-title":"The impact of photobiomodulation therapy on enhancing spermatogenesis and blood-testis barrier integrity in adult male mice subjected to scrotal hyperthermia","volume":"15","author":"Soltani","year":"2024","journal-title":"J Lasers Med Sci"},{"key":"10.1016\/j.xfss.2025.10.001_bib83","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.3390\/ijms25073637","article-title":"The role of heat-induced stress granules in the blood-testis barrier of mice","volume":"25","author":"Zhao","year":"2024","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.xfss.2025.10.001_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2023.114598","article-title":"Arachidonic acid impairs the function of the blood-testis barrier via triggering mitochondrial complex-ROS-P38 MAPK axis in hyperthermal Sertoli cells","volume":"252","author":"Hu","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"10.1016\/j.xfss.2025.10.001_bib85","doi-asserted-by":"crossref","DOI":"10.1111\/and.14169","article-title":"Effect of Wuzi Yanzong Pills on Sertoli cells and blood-testis barrier in heat-stressed rats based on Akt signalling pathway","volume":"53","author":"Xu","year":"2021","journal-title":"Andrologia"},{"key":"10.1016\/j.xfss.2025.10.001_bib86","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1095\/biolreprod.113.109405","article-title":"The heat-induced reversible change in the blood-testis barrier (BTB) is regulated by the androgen receptor (AR) via the partitioning-defective protein (Par) polarity complex in the mouse","volume":"89","author":"Li","year":"2013","journal-title":"Biol Reprod"},{"key":"10.1016\/j.xfss.2025.10.001_bib87","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2024.134126","article-title":"The FAK\/occludin\/ZO-1 complex is critical for cadmium-induced testicular damage by disruption of the integrity of the blood-testis barrier in chickens","volume":"470","author":"Li","year":"2024","journal-title":"J Hazard Mater"},{"key":"10.1016\/j.xfss.2025.10.001_bib88","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12958-024-01204-y","article-title":"Map-1a regulates Sertoli cell BTB dynamics through the cytoskeletal organization of microtubule and F-actin","volume":"22","author":"Wang","year":"2024","journal-title":"Reprod Biol Endocrinol"},{"key":"10.1016\/j.xfss.2025.10.001_bib89","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2024.123625","article-title":"Cross-talk between vimentin and autophagy regulates blood-testis barrier disruption induced by cadmium","volume":"346","author":"Chen","year":"2024","journal-title":"Environ Pollut"},{"key":"10.1016\/j.xfss.2025.10.001_bib90","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2023.167267","article-title":"Molybdenum and cadmium cause blood-testis barrier dysfunction through ROS-mediated NLRP3 inflammasome activation in sheep","volume":"906","author":"Jiang","year":"2024","journal-title":"Sci Total Environ"},{"key":"10.1016\/j.xfss.2025.10.001_bib91","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqad045","article-title":"Cadmium-induced Sertoli cell injury through p38-MAPK and related signaling proteins-a study by RNA sequencing","volume":"164","author":"Wang","year":"2023","journal-title":"Endocrinology"},{"key":"10.1016\/j.xfss.2025.10.001_bib92","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2021.152247","article-title":"Environmental cadmium impairs blood-testis barrier via activating HRI-responsive mitochondrial stress in mice","volume":"810","author":"Zhou","year":"2022","journal-title":"Sci Total Environ"},{"key":"10.1016\/j.xfss.2025.10.001_bib93","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2021.112878","article-title":"Evidence of melatonin ameliorative effects on the blood-testis barrier and sperm quality alterations induced by cadmium in the rat testis","volume":"226","author":"Venditti","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"10.1016\/j.xfss.2025.10.001_bib94","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2019.110142","article-title":"Epigenetic dysregulation of Mdr1b in the blood-testis barrier contributes to dyszoospermia in mice exposed to cadmium","volume":"190","author":"Fang","year":"2020","journal-title":"Ecotoxicol Environ Saf"},{"key":"10.1016\/j.xfss.2025.10.001_bib95","first-page":"245","article-title":"Monitoring the integrity of the blood-testis barrier (BTB): an in vivo assay","volume":"1748","author":"Chen","year":"2018","journal-title":"Methods MolBiol"},{"key":"10.1016\/j.xfss.2025.10.001_bib96","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1210\/en.2002-0211","article-title":"TGF-beta3 regulates the blood-testis barrier dynamics via the p38 mitogen activated protein (MAP) kinase pathway: an in vivo study","volume":"144","author":"Lui","year":"2003","journal-title":"Endocrinology"},{"key":"10.1016\/j.xfss.2025.10.001_bib97","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1095\/biolreprod.112.107284","article-title":"SOX8 regulates permeability of the blood-testes barrier that affects adult male fertility in the mouse","volume":"88","author":"Singh","year":"2013","journal-title":"Biol Reprod"},{"key":"10.1016\/j.xfss.2025.10.001_bib98","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0084354","article-title":"Impaired function of the blood-testis barrier during aging is preceded by a decline in cell adhesion proteins and GTPases","volume":"8","author":"Paul","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.xfss.2025.10.001_bib99","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/j.1939-4640.1999.tb02529.x","article-title":"The effects of aging on the seminiferous epithelium and the blood-testis barrier of the Brown Norway rat","volume":"20","author":"Levy","year":"1999","journal-title":"J Androl"},{"key":"10.1016\/j.xfss.2025.10.001_bib100","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ydbio.2007.05.002","article-title":"Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells","volume":"307","author":"Oakes","year":"2007","journal-title":"Dev Biol"},{"key":"10.1016\/j.xfss.2025.10.001_bib101","doi-asserted-by":"crossref","first-page":"6806","DOI":"10.1073\/pnas.092123699","article-title":"BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma","volume":"99","author":"Loukinov","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.xfss.2025.10.001_bib102","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13072-018-0186-0","article-title":"Transient reduction of DNA methylation at the onset of meiosis in male mice","volume":"11","author":"Gaysinskaya","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"10.1016\/j.xfss.2025.10.001_bib103","article-title":"DNA methylation dynamic in male rat germ cells during gametogenesis","volume":"150","author":"Omri-Charai","year":"2023","journal-title":"Development"},{"key":"10.1016\/j.xfss.2025.10.001_bib104","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/s43587-024-00616-0","article-title":"Nature of epigenetic aging from a single-cell perspective","volume":"4","author":"Tarkhov","year":"2024","journal-title":"Nat Aging"},{"key":"10.1016\/j.xfss.2025.10.001_bib105","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol Cell Proteomics"},{"key":"10.1016\/j.xfss.2025.10.001_bib106","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature13992","article-title":"Mouse ENCODE Consortium. A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"},{"issue":"Suppl 3","key":"10.1016\/j.xfss.2025.10.001_bib107","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/S0015-0282(03)00366-2","article-title":"Effect of male age on fertility: evidence for the decline in male fertility with increasing age","volume":"79","author":"Hassan","year":"2003","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2025.10.001_bib108","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1093\/humrep\/dez223","article-title":"Male ageing is negatively associated with the chance of live birth in IVF\/ICSI cycles for idiopathic infertility","volume":"34","author":"Horta","year":"2019","journal-title":"Hum Reprod"},{"key":"10.1016\/j.xfss.2025.10.001_bib109","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1097\/01.ede.0000142138.46167.69","article-title":"Parental age, family size, and risk of multiple sclerosis","volume":"15","author":"Montgomery","year":"2004","journal-title":"Epidemiology"},{"key":"10.1016\/j.xfss.2025.10.001_bib110","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1177\/1362361311427154","article-title":"Advancing paternal age and simplex autism","volume":"16","author":"Puleo","year":"2012","journal-title":"Autism"},{"key":"10.1016\/j.xfss.2025.10.001_bib111","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.1371\/journal.pmed.1000040","article-title":"Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood","volume":"6","author":"Saha","year":"2009","journal-title":"PLoS Med"},{"key":"10.1016\/j.xfss.2025.10.001_bib112","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.canep.2017.06.010","article-title":"Parental age and childhood cancer risk: a Danish population-based registry study","volume":"49","author":"Contreras","year":"2017","journal-title":"Cancer Epidemiol"},{"key":"10.1016\/j.xfss.2025.10.001_bib113","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/ng.3577","article-title":"Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations","volume":"48","author":"Gratten","year":"2016","journal-title":"Nat Genet"},{"key":"10.1016\/j.xfss.2025.10.001_bib114","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1001\/archpsyc.63.9.1026","article-title":"Advancing paternal age and autism","volume":"63","author":"Reichenberg","year":"2006","journal-title":"Arch Gen Psychiatry"},{"key":"10.1016\/j.xfss.2025.10.001_bib115","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/ajmg.a.34413","article-title":"The importance of advanced parental age in the origin of neurofibromatosis type 1","volume":"158A","author":"Snajderova","year":"2012","journal-title":"Am J Med Genet A"},{"key":"10.1016\/j.xfss.2025.10.001_bib116","doi-asserted-by":"crossref","DOI":"10.15252\/embr.202051524","article-title":"Paternal age affects offspring via an epigenetic mechanism involving REST\/NRSF","volume":"22","author":"Yoshizaki","year":"2021","journal-title":"EMBO Rep"},{"key":"10.1016\/j.xfss.2025.10.001_bib117","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1038\/s41467-023-37820-2","article-title":"Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development","volume":"14","author":"Lismer","year":"2023","journal-title":"Nat Commun"}],"container-title":["F&amp;S Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666335X25000680?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666335X25000680?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:58:03Z","timestamp":1773917883000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666335X25000680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":117,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S2666335X25000680"],"URL":"https:\/\/doi.org\/10.1016\/j.xfss.2025.10.001","relation":{},"ISSN":["2666-335X"],"issn-type":[{"value":"2666-335X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Environmental factors accelerate epigenetic aging of sperm via mechanistic target of rapamycin\/blood-testis barrier mechanism","name":"articletitle","label":"Article Title"},{"value":"F&S Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xfss.2025.10.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}