{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:44:46Z","timestamp":1776761086097,"version":"3.51.2"},"reference-count":96,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stress has been negatively associated with reproductive outcomes, including poor semen quality in men; however, the molecular mechanisms underlying these associations remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to evaluate the association between perceived stress and sperm DNA methylation patterns in men undergoing infertility treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>The study was conducted on 169 men attending the Massachusetts General Hospital Fertility Clinic who provided a semen sample and completed the short version of the Cohen Perceived Stress Scale (PSS\u20104) to quantify perceived psychological stress. Sperm DNA methylation was measured using the Illumina EPIC Array (v1). Associations between stress and DNA methylation were investigated using a linear regression model (CpGassoc) and eXtreme Gradient Boosting (XGBoost), a decision tree\u2010based machine learning approach. The biological relevance of the identified regions was assessed using Metascape.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median (IQR) level of perceived stress reported by the Environment and Reproductive Health (EARTH) Study participants was 4 (3, 6) on the 14\u2010point PSS scale. Perceived stress was associated with 811 differentially methylated CpGs (DMCs;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) in the regression model and 782 CpGs predictive of perceived stress identified by XGBoost. Stress\u2010associated genes were enriched in pathways related to cell morphogenesis, behavior, and neurodevelopment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite not achieving statistical significance after correction for multiple comparisons, our findings nevertheless provide novel insights into reduced fertility potential among men with high levels of perceived stress and highlight DNA methylation as a potential mechanism underlying of paternal epigenetic inheritance of stress\u2010related phenotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70245","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:50:46Z","timestamp":1776757846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Perceived Stress and Sperm DNA Methylation Among Men Attending a Fertility Center"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2370-3900","authenticated-orcid":false,"given":"Lidia","family":"M\u00ednguez\u2010Alarc\u00f3n","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9971-0023","authenticated-orcid":false,"given":"Karolina","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshay G.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Urology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer B.","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramace","family":"Dadd","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge E.","family":"Chavarro","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Department of Nutrition Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russ","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Vincent Obstetrics and Gynecology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4541-6267","authenticated-orcid":false,"given":"J. Richard","family":"Pilsner","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wayne State University School of Medicine  Detroit Michigan USA"},{"name":"Institute of Environmental Health Sciences Wayne State University  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001356"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr501031x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmx022"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2018.10.052"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmac035"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2021.10.020"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu106"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.08.015"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.11.011"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwp168"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwx067"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaf218"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1037\/amp0000597"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/19485560903382338"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912174211033710"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17249248"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010psych\u2010062520\u2010122331"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.04.021"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13301"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2025.02.012"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.10.020"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1654"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.106"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585\u2010022\u201000708\u20109"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep\u201011\u20100450"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41437\u2010025\u201000756\u2010y"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46020101"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201080857\u20102"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12753"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.10.005"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13121750"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.87"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0914\u201013.2013"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429\u2010020\u201002090\u2010x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200322"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2018.00037"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/nur.20284"},{"key":"e_1_2_8_40_1","volume-title":"The Social Psychology of Health","author":"Cohen S.","year":"1988"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey259"},{"key":"e_1_2_8_42_1","volume-title":"World Health Organization. Laboratory Manual for the Examination and Processing of Human Semen","author":"WHO","year":"2010"},{"issue":"1","key":"e_1_2_8_43_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0015-0282(16)59660-5","article-title":"Predictive Value of Abnormal Sperm Morphology in In Vitro Fertilization","volume":"49","author":"Kruger T. F.","year":"1988","journal-title":"Fertility and Sterility"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.2144\/000114280"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac084"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.109049"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw285"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt090"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20108935\u20108\u20106"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts034"},{"key":"e_1_2_8_52_1","volume-title":"RStudio: Integrated Development Environment for R","author":"Team P","year":"2022"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts124"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/gco.0000000000000069"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20107827\u201011\u201066"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104956"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1080\/19396368.2018.1434838"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v025.i01"},{"key":"e_1_2_8_59_1","unstructured":"A.KassambaraandF.Mundt Factoextra: Extract and Visualize the Results of Multivariate Data Analyses(CRAN 2020)."},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.00731"},{"key":"e_1_2_8_61_1","doi-asserted-by":"crossref","unstructured":"T. G.Chen \u201cC. XGBoost: A Scalable Tree Boosting System \u201dpaper presented at KDD '16: Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining San Francisco USA August 13\u201317 2016.","DOI":"10.1145\/2939672.2939785"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256\u2010019\u20100138\u20109"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009234\u20106"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294236"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts277"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.01.019"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa606"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201033268\u2010y"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3138"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19030256"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512172"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12362"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2017.05.010"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2018.05.014"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2022.101330"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010020\u201000974\u20107"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.151650"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.114115"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dex283"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2025.127227"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1071\/rd10326"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719116650755"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010024\u201002872\u20103"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010018\u20100252\u20101"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.19058"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.09.013"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2021.106693"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108577"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.05.036"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010018\u20100146\u20102"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3594"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.09.013"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1111\/dgd.12668"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.04.06.647459"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2017.1322575"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70245","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.70245","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70245","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T07:50:49Z","timestamp":1776757849000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.70245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":96,"alternative-id":["10.1111\/andr.70245"],"URL":"https:\/\/doi.org\/10.1111\/andr.70245","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"assertion":[{"value":"2026-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"andr.70245"}}