{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:47:05Z","timestamp":1790135225341,"version":"4.0.1"},"reference-count":115,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T00:00:00Z","timestamp":1611360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Institute of Environmental Sciences","award":["R01 ES024478"],"award-info":[{"award-number":["R01 ES024478"]}]},{"name":"National Institute of Environmental Sciences","award":["1R01 ES031846"],"award-info":[{"award-number":["1R01 ES031846"]}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["P30 ES026529"],"award-info":[{"award-number":["P30 ES026529"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cadmium exposure is ubiquitous and has been linked to diseases including cancers and reproductive defects. Since cadmium is nonmutagenic, it is thought to exert its gene dysregulatory effects through epigenetic reprogramming. Several studies have implicated germline exposure to cadmium in developmental reprogramming. However, most of these studies have focused on maternal exposure, while the impact on sperm fertility and disease susceptibility has received less attention. In this study, we used reduced representation bisulfite sequencing to comprehensively investigate the impact of chronic cadmium exposure on mouse spermatozoa DNA methylation. Adult male C57BL\/J6 mice were provided water with or without cadmium chloride for 9 weeks. Sperm, testes, liver, and kidney tissues were collected at the end of the treatment period. Cadmium exposure was confirmed through gene expression analysis of metallothionein-1 and 2, 2 well-known cadmium-induced genes. Analysis of sperm DNA methylation changes revealed 1788 differentially methylated sites present at regulatory regions in sperm of mice exposed to cadmium compared with vehicle (control) mice. Furthermore, most of these differential methylation changes positively correlated with changes in gene expression at both the transcription initiation stage as well as the splicing levels. Interestingly, the genes targeted by cadmium exposure are involved in several critical developmental processes. Our results present a comprehensive analysis of the sperm methylome in response to chronic cadmium exposure. These data, therefore, highlight a foundational framework to study gene expression patterns that may affect fertility in the exposed individual as well as their offspring, through paternal inheritance.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab002","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T17:25:06Z","timestamp":1609953906000},"page":"262-276","source":"Crossref","is-referenced-by-count":31,"title":["Chronic Exposure to Cadmium Induces Differential Methylation in Mice Spermatozoa"],"prefix":"10.1093","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1032-6202","authenticated-orcid":false,"given":"Wesley N","family":"Saintilnord","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536-0509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Y N","family":"Tenlep","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536-0509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D","family":"Preston","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536-0509, USA"},{"name":"Emory University School of Medicine, Atlanta, Georgia 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Duregon","sequence":"additional","affiliation":[{"name":"Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason E","family":"DeRouchey","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington, Kentucky 40536-0509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M","family":"Unrine","sequence":"additional","affiliation":[{"name":"Department of Plant and Soil Sciences, University of Kentucky, Lexington, Kentucky 40536-0509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"de Cabo","sequence":"additional","affiliation":[{"name":"Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J","family":"Pearson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536-0509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne N","family":"Fondufe-Mittendorf","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536-0509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,23]]},"reference":[{"key":"2021041221224966700_kfab002-B1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12958-016-0177-6","article-title":"Sperm motility and morphology changes in rats exposed to cadmium and diazinon","volume":"14","author":"Adamkovicova","year":"2016","journal-title":"Reprod. Biol. Endocrinol"},{"key":"2021041221224966700_kfab002-B2","doi-asserted-by":"crossref","first-page":"R87","DOI":"10.1186\/gb-2012-13-10-r87","article-title":"Methylkit: A comprehensive R package for the analysis of genome-wide DNA methylation profiles","volume":"13","author":"Akalin","year":"2012","journal-title":"Genome Biol"},{"key":"2021041221224966700_kfab002-B3","doi-asserted-by":"crossref","first-page":"6435","DOI":"10.1158\/0008-5472.CAN-08-0329","article-title":"Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: A population-based prospective cohort study","volume":"68","author":"Akesson","year":"2008","journal-title":"Cancer Res"},{"key":"2021041221224966700_kfab002-B4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13072-018-0205-1","article-title":"Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species","volume":"11","author":"Anastasiadi","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"2021041221224966700_kfab002-B5","author":"Andrews","year":"2010"},{"key":"2021041221224966700_kfab002-B6","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1039\/b903049b","article-title":"Epigenetics in metal carcinogenesis: Nickel, arsenic, chromium and cadmium","volume":"1","author":"Arita","year":"2009","journal-title":"Metallomics"},{"key":"2021041221224966700_kfab002-B7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev"},{"key":"2021041221224966700_kfab002-B8","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/ng.708","article-title":"Targets and dynamics of promoter DNA methylation during early mouse development","volume":"42","author":"Borgel","year":"2010","journal-title":"Nat. Genet"},{"key":"2021041221224966700_kfab002-B9","doi-asserted-by":"crossref","first-page":"31368","DOI":"10.1007\/s11356-019-06248-x","article-title":"Decreased total sperm counts in habitants of highly polluted areas of Eastern Sicily, Italy","volume":"26","author":"Cannarella","year":"2019","journal-title":"Environ. Sci. Pollut. Res. Int"},{"key":"2021041221224966700_kfab002-B10","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.cell.2010.12.008","article-title":"Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals","volume":"143","author":"Carone","year":"2010","journal-title":"Cell"},{"key":"2021041221224966700_kfab002-B11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.devcel.2014.05.024","article-title":"High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm","volume":"30","author":"Carone","year":"2014","journal-title":"Dev. Cell"},{"key":"2021041221224966700_kfab002-B12","first-page":"328","article-title":"Endocrinologic and immunologic function in uremic patients with asthenia of the kidney","volume":"3","author":"Chen","year":"1983","journal-title":"Zhong Xi Yi Jie He Za Zhi"},{"key":"2021041221224966700_kfab002-B13","doi-asserted-by":"crossref","first-page":"037003","DOI":"10.1289\/EHP2085","article-title":"Effects of cadmium exposure on DNA methylation at imprinting control regions and genome-wide in mothers and newborn children","volume":"126","author":"Cowley","year":"2018","journal-title":"Environ. Health Perspect"},{"key":"2021041221224966700_kfab002-B14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/019262339702500201","article-title":"Evaluation of testicular toxicity in safety evaluation studies: The appropriate use of spermatogenic staging","volume":"25","author":"Creasy","year":"1997","journal-title":"Toxicol. Pathol"},{"key":"2021041221224966700_kfab002-B15","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.3390\/ijms21134704","article-title":"A \u201cpopulation dynamics\u201d perspective on the delayed life-history effects of environmental contaminations: An illustration with a preliminary study of cadmium transgenerational effects over three generations in the Crustacean Gammarus","volume":"21","author":"Cribiu","year":"2020","journal-title":"Int. J. Mol. Sci"},{"key":"2021041221224966700_kfab002-B16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1165\/rcmb.2014-0160OC","article-title":"Alterations in gene expression and DNA methylation during murine and human lung alveolar septation","volume":"53","author":"Cuna","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2021041221224966700_kfab002-B17","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1093\/hmg\/9.19.2885","article-title":"The h19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development","volume":"9","author":"Davis","year":"2000","journal-title":"Hum. Mol. Genet"},{"key":"2021041221224966700_kfab002-B18","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nrg3188","article-title":"Understanding transgenerational epigenetic inheritance via the gametes in mammals","volume":"13","author":"Daxinger","year":"2012","journal-title":"Nat. Rev. Genet"},{"key":"2021041221224966700_kfab002-B19","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.molmet.2015.12.002","article-title":"High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring","volume":"5","author":"de Castro Barbosa","year":"2016","journal-title":"Mol. Metab"},{"key":"2021041221224966700_kfab002-B20","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1101\/gad.2037511","article-title":"CpG islands and the regulation of transcription","volume":"25","author":"Deaton","year":"2011","journal-title":"Genes Dev"},{"key":"2021041221224966700_kfab002-B21","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.fct.2017.09.002","article-title":"Maternal cadmium exposure and impact on foetal gene expression through methylation changes","volume":"109","author":"Dharmadasa","year":"2017","journal-title":"Food Chem. Toxicol"},{"key":"2021041221224966700_kfab002-B22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nn.3594","article-title":"Parental olfactory experience influences behavior and neural structure in subsequent generations","volume":"17","author":"Dias","year":"2014","journal-title":"Nat. Neurosci"},{"key":"2021041221224966700_kfab002-B23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.taap.2017.03.017","article-title":"Transient and permanent changes in DNA methylation patterns in inorganic arsenic-mediated epithelial-to-mesenchymal transition","volume":"331","author":"Eckstein","year":"2017","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2021041221224966700_kfab002-B24","year":"2020"},{"key":"2021041221224966700_kfab002-B25","doi-asserted-by":"crossref","first-page":"e100815","DOI":"10.1371\/journal.pone.0100815","article-title":"Dietary cadmium intake and risk of breast, endometrial and ovarian cancer in Danish postmenopausal women: A prospective cohort study","volume":"9","author":"Eriksen","year":"2014","journal-title":"PLoS One"},{"key":"2021041221224966700_kfab002-B26","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.3390\/ijerph17113782","article-title":"The effects of cadmium toxicity","volume":"17","author":"Genchi","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"2021041221224966700_kfab002-B27","doi-asserted-by":"crossref","first-page":"148","DOI":"10.5534\/wjmh.180071","article-title":"Epigenetics of male fertility: Effects on assisted reproductive techniques","volume":"37","author":"Giacone","year":"2019","journal-title":"World J. Mens Health"},{"key":"2021041221224966700_kfab002-B28","doi-asserted-by":"crossref","first-page":"e13100","DOI":"10.1371\/journal.pone.0013100","article-title":"Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome","volume":"5","author":"Guerrero-Bosagna","year":"2010","journal-title":"PLoS One"},{"key":"2021041221224966700_kfab002-B29","doi-asserted-by":"crossref","first-page":"e1007766","DOI":"10.1371\/journal.pgen.1007766","article-title":"Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity","volume":"14","author":"Hahn","year":"2018","journal-title":"PLoS Genet"},{"key":"2021041221224966700_kfab002-B30","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nature08162","article-title":"Distinctive chromatin in human sperm packages genes for embryo development","volume":"460","author":"Hammoud","year":"2009","journal-title":"Nature"},{"key":"2021041221224966700_kfab002-B31","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1095\/biolreprod66.3.735","article-title":"Samp32, a testis-specific, isoantigenic sperm acrosomal membrane-associated protein","volume":"66","author":"Hao","year":"2002","journal-title":"Biol. Reprod"},{"key":"2021041221224966700_kfab002-B32","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1038\/nprot.2016.117","article-title":"Analyzing and interpreting genome data at the network level with ConsensusPathDB","volume":"11","author":"Herwig","year":"2016","journal-title":"Nat. Protoc"},{"key":"2021041221224966700_kfab002-B33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1095\/biolreprod.114.126326","article-title":"Processive pulses of retinoic acid propel asynchronous and continuous murine sperm production","volume":"92","author":"Hogarth","year":"2015","journal-title":"Biol. Reprod"},{"key":"2021041221224966700_kfab002-B34","doi-asserted-by":"crossref","first-page":"12982","DOI":"10.1038\/srep12982","article-title":"Deletion of the tyrosine phosphatase Shp2 in Sertoli cells causes infertility in mice","volume":"5","author":"Hu","year":"2015","journal-title":"Sci. Rep"},{"key":"2021041221224966700_kfab002-B35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4103\/0974-1208.97798","article-title":"Testicular toxicity and sperm quality following cadmium exposure in rats: Ameliorative potentials of Allium cepa","volume":"5","author":"Ige","year":"2012","journal-title":"J. Hum. Reprod. Sci"},{"key":"2021041221224966700_kfab002-B36","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/ng.298","article-title":"The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores","volume":"41","author":"Irizarry","year":"2009","journal-title":"Nat. Genet"},{"key":"2021041221224966700_kfab002-B37","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":"2021041221224966700_kfab002-B38","doi-asserted-by":"crossref","first-page":"460","DOI":"10.2337\/db08-0490","article-title":"Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice","volume":"58","author":"Jimenez-Chillaron","year":"2009","journal-title":"Diabetes"},{"key":"2021041221224966700_kfab002-B39","doi-asserted-by":"crossref","first-page":"462","DOI":"10.18632\/oncotarget.497","article-title":"On the presence and role of human gene-body DNA methylation","volume":"3","author":"Jjingo","year":"2012","journal-title":"Oncotarget"},{"key":"2021041221224966700_kfab002-B40","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0168-9525(98)01636-9","article-title":"The DNA methylation paradox","volume":"15","author":"Jones","year":"1999","journal-title":"Trends Genet"},{"key":"2021041221224966700_kfab002-B41","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1158\/0008-5472.CAN-11-0735","article-title":"Dietary cadmium exposure and risk of postmenopausal breast cancer: A population-based prospective cohort study","volume":"72","author":"Julin","year":"2012","journal-title":"Cancer Res"},{"key":"2021041221224966700_kfab002-B42","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/bjc.2012.311","article-title":"Dietary cadmium exposure and prostate cancer incidence: A population-based prospective cohort study","volume":"107","author":"Julin","year":"2012","journal-title":"Br. J. Cancer"},{"key":"2021041221224966700_kfab002-B43","doi-asserted-by":"crossref","first-page":"D793","DOI":"10.1093\/nar\/gks1055","article-title":"The ConsensusPathDB interaction database: 2013 update","volume":"41(Database issue","author":"Kamburov","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2021041221224966700_kfab002-B44","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3389\/fcell.2019.00195","article-title":"Mechanism of acrosome biogenesis in mammals","volume":"7","author":"Khawar","year":"2019","journal-title":"Front. Cell Dev. Biol"},{"key":"2021041221224966700_kfab002-B45","doi-asserted-by":"crossref","first-page":"e322","DOI":"10.1038\/emm.2017.10","article-title":"DNA methylation: An epigenetic mark of cellular memory","volume":"49","author":"Kim","year":"2017","journal-title":"Exp. Mol. Med"},{"key":"2021041221224966700_kfab002-B46","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2131\/jts.44.309","article-title":"Long-term cadmium exposure enhances metallothionein-1 induction after subsequent exposure to high concentrations of cadmium in p1798 mouse lymphosarcoma cells","volume":"44","author":"Kimura","year":"2019","journal-title":"J. Toxicol. Sci"},{"key":"2021041221224966700_kfab002-B47","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.taap.2017.05.033","article-title":"Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish","volume":"329","author":"Knecht","year":"2017","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2021041221224966700_kfab002-B48","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S0140-6736(77)90714-0","article-title":"Cadmium and prostatic carcinoma","volume":"310","author":"Kolonel","year":"1977","journal-title":"Lancet"},{"key":"2021041221224966700_kfab002-B49","author":"Krueger"},{"key":"2021041221224966700_kfab002-B50","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","article-title":"Bismark: A flexible aligner and methylation caller for bisulfite-seq applications","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics"},{"key":"2021041221224966700_kfab002-B511","doi-asserted-by":"crossref","first-page":"e69927","DOI":"10.1371\/journal.pone.0069927","article-title":"Semen abnormalities, sperm DNA damage and global hypermethylation in health workers occupationally exposed to ionizing radiation","volume":"8","author":"Kumar","year":"2013","journal-title":"PLoS One"},{"key":"2021041221224966700_kfab002-B52","doi-asserted-by":"crossref","first-page":"e6953","DOI":"10.1371\/journal.pone.0006953","article-title":"Insulin gene expression is regulated by DNA methylation","volume":"4","author":"Kuroda","year":"2009","journal-title":"PLoS One"},{"key":"2021041221224966700_kfab002-B53","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/01926230290105695","article-title":"Recommended approaches for the evaluation of testicular and epididymal toxicity","volume":"30","author":"Lanning","year":"2002","journal-title":"Toxicol. Pathol"},{"key":"2021041221224966700_kfab002-B54","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/em.21874","article-title":"Exposure to perfluoroalkyl substances and sperm DNA global methylation in arctic and European populations","volume":"55","author":"Leter","year":"2014","journal-title":"Environ. Mol. Mutagen"},{"key":"2021041221224966700_kfab002-B55","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tig.2015.03.002","article-title":"The alternative role of DNA methylation in splicing regulation","volume":"31","author":"Lev Maor","year":"2015","journal-title":"Trends Genet"},{"key":"2021041221224966700_kfab002-B56","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1073\/pnas.1620519114","article-title":"Cerberus-Nodal-Lefty-Pitx signaling cascade controls left-right asymmetry in amphioxus","volume":"114","author":"Li","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021041221224966700_kfab002-B57","doi-asserted-by":"crossref","first-page":"985","DOI":"10.4103\/1008-682X.160267","article-title":"Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring","volume":"17","author":"Liang","year":"2015","journal-title":"Asian J. Androl"},{"key":"2021041221224966700_kfab002-B58","doi-asserted-by":"crossref","first-page":"110006","DOI":"10.1016\/j.ecoenv.2019.110006","article-title":"Associations of plasma metal concentrations with the decline in kidney function: A longitudinal study of Chinese adults","volume":"189","author":"Liu","year":"2020","journal-title":"Ecotoxicol. Environ. Saf"},{"key":"2021041221224966700_kfab002-B59","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":"2021041221224966700_kfab002-B60","doi-asserted-by":"crossref","first-page":"16786","DOI":"10.1038\/s41598-019-52903-1","article-title":"Sperm DNA methylation epimutation biomarkers for male infertility and FSH therapeutic responsiveness","volume":"9","author":"Luj\u00e1n","year":"2019","journal-title":"Sci. Rep"},{"key":"2021041221224966700_kfab002-B61","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1095\/biolreprod.116.144113","article-title":"Kinesins in spermatogenesis","volume":"96","author":"Ma","year":"2017","journal-title":"Biol. Reprod"},{"key":"2021041221224966700_kfab002-B62","doi-asserted-by":"crossref","first-page":"e46249","DOI":"10.1371\/journal.pone.0046249","article-title":"Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations","volume":"7","author":"Manikkam","year":"2012","journal-title":"PLoS One"},{"key":"2021041221224966700_kfab002-B63","doi-asserted-by":"crossref","first-page":"e55387","DOI":"10.1371\/journal.pone.0055387","article-title":"Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations","volume":"8","author":"Manikkam","year":"2013","journal-title":"PLoS One"},{"key":"2021041221224966700_kfab002-B64","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1136\/thorax.2003.012054","article-title":"Urinary cadmium levels predict lower lung function in current and former smokers: Data from the third national health and nutrition examination survey","volume":"59","author":"Mannino","year":"2004","journal-title":"Thorax"},{"key":"2021041221224966700_kfab002-B65","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/cr.2013.110","article-title":"Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition","volume":"23","author":"Maunakea","year":"2013","journal-title":"Cell Res"},{"key":"2021041221224966700_kfab002-B66","first-page":"35","article-title":"Chromosomal abnormality in men with impaired spermatogenesis","volume":"8","author":"Mierla","year":"2014","journal-title":"Int. J. Fertil. Steril"},{"key":"2021041221224966700_kfab002-B67","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.envres.2015.02.004","article-title":"Infant sex-specific placental cadmium and DNA methylation associations","volume":"138","author":"Mohanty","year":"2015","journal-title":"Environ. Res"},{"key":"2021041221224966700_kfab002-B68","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1080\/15592294.2018.1554521","article-title":"Cannabinoid exposure and altered DNA methylation in rat and human sperm","volume":"13","author":"Murphy","year":"2018","journal-title":"Epigenetics"},{"key":"2021041221224966700_kfab002-B69","first-page":"343","article-title":"IGF-I, IGF-II and insulin promote differentiation of spermatogonia to primary spermatocytes in organ culture of newt testes","volume":"43","author":"Nakayama","year":"1999","journal-title":"Int. J. Dev. Biol"},{"key":"2021041221224966700_kfab002-B70","volume-title":"Report on Carcinogens","year":"2016","edition":"14th edn"},{"key":"2021041221224966700_kfab002-B71","doi-asserted-by":"crossref","first-page":"dvy016","DOI":"10.1093\/eep\/dvy016","article-title":"Environmentally induced epigenetic transgenerational inheritance of disease","volume":"4","author":"Nilsson","year":"2018","journal-title":"Environ. Epigenet"},{"key":"2021041221224966700_kfab002-B72","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.taap.2009.03.015","article-title":"Historical perspectives on cadmium toxicology","volume":"238","author":"Nordberg","year":"2009","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2021041221224966700_kfab002-B73","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.biochi.2009.06.014","article-title":"Prevalence of kidney dysfunction in humans - Relationship to cadmium dose, metallothionein, immunological and metabolic factors","volume":"91","author":"Nordberg","year":"2009","journal-title":"Biochimie"},{"key":"2021041221224966700_kfab002-B74","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.reprotox.2009.08.001","article-title":"Adverse effects of cadmium exposure on mouse sperm","volume":"28","author":"Oliveira","year":"2009","journal-title":"Reprod. Toxicol"},{"key":"2021041221224966700_kfab002-B75","doi-asserted-by":"crossref","first-page":"R173","DOI":"10.1530\/REP-17-0018","article-title":"Obesity, energy balance and spermatogenesis","volume":"153","author":"Oliveira","year":"2017","journal-title":"Reproduction"},{"key":"2021041221224966700_kfab002-B76","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":"2021041221224966700_kfab002-B77","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1006\/bbrc.2001.4805","article-title":"Cloning and expression of activator of CREM in testis in human testicular tissue","volume":"283","author":"Palermo","year":"2001","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2021041221224966700_kfab002-B78","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.sab.2006.09.001","article-title":"Determination of lead, cadmium and mercury in blood for assessment of environmental exposure: A comparison between inductively coupled plasma\u2013mass spectrometry and atomic absorption spectrometry","volume":"61","author":"Palmer","year":"2006","journal-title":"Spectrochim. Acta B Atom. Spectrosc"},{"key":"2021041221224966700_kfab002-B79","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2147\/CMAR.S171200","article-title":"Chronic cadmium exposure aggravates malignant phenotypes of nasopharyngeal carcinoma by activating the Wnt\/beta-catenin signaling pathway via hypermethylation of the casein kinase 1alpha promoter","volume":"11","author":"Peng","year":"2018","journal-title":"Cancer Manag. Res"},{"key":"2021041221224966700_kfab002-B80","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1439-0531.2004.00532.x","article-title":"In vitro sperm penetration speed and its relationship with in vivo bull fertility","volume":"39","author":"Puglisi","year":"2004","journal-title":"Reprod. Domest. Anim"},{"key":"2021041221224966700_kfab002-B81","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/stem.1572","article-title":"The transition from stem cell to progenitor spermatogonia and male fertility requires the shp2 protein tyrosine phosphatase","volume":"32","author":"Puri","year":"2014","journal-title":"Stem Cells"},{"key":"2021041221224966700_kfab002-B82","doi-asserted-by":"crossref","first-page":"41474","DOI":"10.1038\/srep41474","article-title":"Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformation","volume":"7","author":"Rea","year":"2017","journal-title":"Sci. Rep"},{"key":"2021041221224966700_kfab002-B83","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/onc.2008.478","article-title":"Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration","volume":"28","author":"Sagara","year":"2009","journal-title":"Oncogene"},{"key":"2021041221224966700_kfab002-B84","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.devcel.2014.05.023","article-title":"Uniformity of nucleosome preservation pattern in mammalian sperm and its connection to repetitive DNA elements","volume":"30","author":"Samans","year":"2014","journal-title":"Dev. Cell"},{"key":"2021041221224966700_kfab002-B85","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4161\/epi.26798","article-title":"Cadmium exposure and the epigenome: Exposure-associated patterns of DNA methylation in leukocytes from mother-baby pairs","volume":"9","author":"Sanders","year":"2014","journal-title":"Epigenetics"},{"key":"2021041221224966700_kfab002-B86","doi-asserted-by":"crossref","first-page":"692","DOI":"10.4161\/epi.6.6.16196","article-title":"Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome","volume":"6","author":"Sandoval","year":"2011","journal-title":"Epigenetics"},{"key":"2021041221224966700_kfab002-B87","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2174\/138920012799320446","article-title":"Long-term exposure to cadmium in food and cigarette smoke, liver effects and hepatocellular carcinoma","volume":"13","author":"Satarug","year":"2012","journal-title":"Curr. Drug Metab"},{"key":"2021041221224966700_kfab002-B88","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1073\/pnas.0510310103","article-title":"A genome-wide analysis of CPG dinucleotides in the human genome distinguishes two distinct classes of promoters","volume":"103","author":"Saxonov","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021041221224966700_kfab002-B89","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(t) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc"},{"key":"2021041221224966700_kfab002-B90","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ygcen.2009.02.013","article-title":"Spermatogenesis in fish","volume":"165","author":"Schulz","year":"2010","journal-title":"Gen. Comp. Endocrinol"},{"key":"2021041221224966700_kfab002-B91","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nature10442","article-title":"CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing","volume":"479","author":"Shukla","year":"2011","journal-title":"Nature"},{"key":"2021041221224966700_kfab002-B92","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.taap.2009.01.028","article-title":"Cadmium-induced testicular injury","volume":"238","author":"Siu","year":"2009","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2021041221224966700_kfab002-B93","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1080\/15592294.2019.1614417","article-title":"Transgenerational sperm DNA methylation epimutation developmental origins following ancestral vinclozolin exposure","volume":"14","author":"Skinner","year":"2019","journal-title":"Epigenetics"},{"key":"2021041221224966700_kfab002-B94","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/ijo.2013.193","article-title":"Newborns of obese parents have altered DNA methylation patterns at imprinted genes","volume":"39","author":"Soubry","year":"2015","journal-title":"Int. J. Obes. (Lond"},{"key":"2021041221224966700_kfab002-B95","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1741-7015-11-29","article-title":"Paternal obesity is associated with IGF2 hypomethylation in newborns: Results from a newborn epigenetics study (NEST) cohort","volume":"11","author":"Soubry","year":"2013","journal-title":"BMC Med"},{"key":"2021041221224966700_kfab002-B96","first-page":"447","article-title":"A quantitative assessment of lung cancer risk and occupational cadmium exposure","author":"Stayner","year":"1992","journal-title":"IARC Sci. Publ"},{"key":"2021041221224966700_kfab002-B97","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.reprotox.2011.02.009","article-title":"Prenatal exposure to ethanol: A specific effect on the h19 gene in sperm","volume":"31","author":"Stouder","year":"2011","journal-title":"Reprod. Toxicol"},{"key":"2021041221224966700_kfab002-B98","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0014-4827(03)00062-4","article-title":"Effects of cadmium on DNA-(cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation","volume":"286","author":"Takiguchi","year":"2003","journal-title":"Exp. Cell Res"},{"key":"2021041221224966700_kfab002-B99","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00418-005-0031-y","article-title":"Immunohistochemical study of a membrane skeletal molecule, protein 4.1g, in mouse seminiferous tubules","volume":"124","author":"Terada","year":"2005","journal-title":"Histochem. Cell Biol"},{"key":"2021041221224966700_kfab002-B100","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nmeth.f.391","article-title":"Diagenode\u00ae premium RRBS technology: Cost-effective DNA methylation mapping with superior coverage","volume":"13","author":"Veillard","year":"2016","journal-title":"Nat. Methods"},{"key":"2021041221224966700_kfab002-B101","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.4161\/epi.22446","article-title":"PGE2 induces interleukin-8 derepression in human astrocytoma through coordinated DNA demethylation and histone hyperacetylation","volume":"7","author":"Venza","year":"2012","journal-title":"Epigenetics"},{"key":"2021041221224966700_kfab002-B102","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10815-012-9921-9","article-title":"Balanced chromosomal translocations in men: Relationships among semen parameters, chromatin integrity, sperm meiotic segregation and aneuploidy","volume":"30","author":"Vozdova","year":"2013","journal-title":"J. Assist. Reprod. Genet"},{"key":"2021041221224966700_kfab002-B103","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1095\/biolreprod.109.077107","article-title":"A novel, single, transmembrane protein CATSPERG is associated with CATSPER1 channel protein","volume":"81","author":"Wang","year":"2009","journal-title":"Biol. Reprod"},{"key":"2021041221224966700_kfab002-B104","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000477113","article-title":"Exposure to cadmium impairs sperm functions by reducing CATSPER in mice","volume":"42","author":"Wang","year":"2017","journal-title":"Cell Physiol. Biochem"},{"key":"2021041221224966700_kfab002-B105","doi-asserted-by":"crossref","first-page":"15825","DOI":"10.1038\/s41598-018-34149-5","article-title":"Transcriptome dynamics during turbot spermatogenesis predicting the potential key genes regulating male germ cell proliferation and maturation","volume":"8","author":"Wang","year":"2018","journal-title":"Sci. Rep"},{"key":"2021041221224966700_kfab002-B106","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0070-2153(05)71008-5","article-title":"The blood-testis barrier: Its biology, regulation, and physiological role in spermatogenesis","volume":"71","author":"Wong","year":"2005","journal-title":"Curr. Top. Dev. Biol"},{"key":"2021041221224966700_kfab002-B107","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1242\/jcs.00900","article-title":"Regulation of blood-testis barrier dynamics: An in vivo study","volume":"117","author":"Wong","year":"2004","journal-title":"J. Cell Sci"},{"key":"2021041221224966700_kfab002-B108","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.gene.2018.06.020","article-title":"The characterization and potential roles of bone morphogenetic protein 7 during spermatogenesis in Chinese mitten crab Eriocheir sinensis","volume":"673","author":"Xu","year":"2018","journal-title":"Gene"},{"key":"2021041221224966700_kfab002-B109","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.12659\/MSM.911170","article-title":"Clinical features of chromosome 6 translocation in male carriers: A report of 10 cases and review of the literature","volume":"24","author":"Yang","year":"2018","journal-title":"Med. Sci. Monit"},{"key":"2021041221224966700_kfab002-B110","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.envres.2019.01.007","article-title":"Differential DNA methylation in newborns with maternal exposure to heavy metals from an e-waste recycling area","volume":"171","author":"Zeng","year":"2019","journal-title":"Environ. Res"},{"key":"2021041221224966700_kfab002-B111","doi-asserted-by":"crossref","first-page":"16178","DOI":"10.4238\/2015.December.8.7","article-title":"Genetic screening and evaluation for chromosomal abnormalities of infertile males in Jilin province, China","volume":"14","author":"Zhang","year":"2015","journal-title":"Genet. Mol. Res"},{"key":"2021041221224966700_kfab002-B112","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.3389\/fgene.2019.01001","article-title":"Association of sperm methylation at line-1, four candidate genes, and nicotine\/alcohol exposure with the risk of infertility","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Genet"},{"key":"2021041221224966700_kfab002-B113","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.ajhg.2012.04.001","article-title":"A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia","volume":"90","author":"Zhao","year":"2012","journal-title":"Am. J. Hum. Genet"},{"key":"2021041221224966700_kfab002-B114","doi-asserted-by":"crossref","first-page":"e0186727","DOI":"10.1371\/journal.pone.0186727","article-title":"Reproductive effects of cadmium on sperm function and early embryonic development in vitro","volume":"12","author":"Zhao","year":"2017","journal-title":"PLoS One"},{"key":"2021041221224966700_kfab002-B115","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"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfab002\/36154038\/kfab002.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/180\/2\/262\/37037220\/kfab002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/180\/2\/262\/37037220\/kfab002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T17:27:23Z","timestamp":1618248443000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/180\/2\/262\/6112042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,23]]},"references-count":115,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1,23]]},"published-print":{"date-parts":[[2021,4,12]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfab002","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,4,1]]},"published":{"date-parts":[[2021,1,23]]}}}