{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T20:39:07Z","timestamp":1786653547794,"version":"build-2736575974"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Lead (Pb) exposure is a risk factor of male infertility, while the transcriptional and epigenetic changes associated with lead exposure in spermatozoa are poorly understood. Our previous findings revealed significant changes in DNA methylation of the calcium (Ca) homeostasis pathway of human spermatozoa in men with a blood Pb level over 5 \u00b5g dl\n                    <jats:sup>\u22121<\/jats:sup>\n                    , which was associated with decreased sperm motility. In this study, we explored the effects of Pb exposure on expression of differentially methylated genes (DMGs) by analyzing semen samples from six healthy, non-smoking, and non-drinking men (aged 20\u201340 years). Using methylated DNA immunoprecipitation sequencing (MeDIP-seq) and RNA sequencing (RNA-seq), we compared DNA methylation and RNA abundance patterns between two groups: three men with blood Pb level 0\u20132.5 \u00b5g dl\n                    <jats:sup>\u22121<\/jats:sup>\n                    and three men with blood Pb level 5\u201310 \u00b5g dl\n                    <jats:sup>\u22121<\/jats:sup>\n                    . Additionally, we experimentally validated the regulatory function of the differentially methylated regions associated with 11 hub genes using dual-luciferase reporter assays. We revealed differences in promoter activity between methylated and unmethylated promoter regions of seven cloned genes, namely calcium voltage-gated channel subunit alpha1 H (\n                    <jats:italic toggle=\"yes\">CACNA1H<\/jats:italic>\n                    ), calcium voltage-gated channel subunit alpha1 G (\n                    <jats:italic toggle=\"yes\">CACNA1G<\/jats:italic>\n                    ), calcium voltage-gated channel subunit alpha1 I (\n                    <jats:italic toggle=\"yes\">CACNA1I<\/jats:italic>\n                    ), calcium\/calmodulin dependent protein kinase II gamma (\n                    <jats:italic toggle=\"yes\">CAMK2G<\/jats:italic>\n                    ), ATPase sarcoplasmic\/endoplasmic reticulum Ca\u00b2\n                    <jats:sup>+<\/jats:sup>\n                    transporting 3 (\n                    <jats:italic toggle=\"yes\">ATP2A3<\/jats:italic>\n                    ), solute carrier family 8 member A2 (\n                    <jats:italic toggle=\"yes\">SLC8A2<\/jats:italic>\n                    ), and glutamate ionotropic receptor NMDA type subunit 2D (\n                    <jats:italic toggle=\"yes\">GRIN2D<\/jats:italic>\n                    ). Our results of Pb exposure-induced expression changes of essential genes associated with the calcium signaling pathway, particularly\n                    <jats:italic toggle=\"yes\">CACNA1H<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SLC8A2,<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">GRIN2D<\/jats:italic>\n                    , in spermatozoa, may be a potential cause of low sperm quality.\n                  <\/jats:p>","DOI":"10.4103\/aja202563","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T12:00:09Z","timestamp":1768305609000},"page":"297-303","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional and epigenetic changes associated with lead exposure in spermatozoa"],"prefix":"10.4103","volume":"28","author":[{"given":"Xu","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Reproduction Regulation of National Health Commission, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Rong","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproduction Regulation of National Health Commission, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproduction Regulation of National Health Commission, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproduction Regulation of National Health Commission, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Juan","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproduction Regulation of National Health Commission, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Reproduction Regulation of National Health Commission, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"R1-20260430","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1177\/0960327117737146","article-title":"Historical documentation of lead toxicity prior to the 20th century in English literature","volume":"37","author":"Jonasson","year":"2018","journal-title":"Hum Exp Toxicol"},{"key":"R2-20260430","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2105\/AJPH.94.1.8","article-title":"What level of lead in blood is toxic for a child?","volume":"94","author":"Needleman","year":"2004","journal-title":"Am J Public Health"},{"key":"R3-20260430","first-page":"1077","article-title":"Occupational lead poisoning","volume":"58","author":"Sokas","year":"1998","journal-title":"Am Fam Physician"},{"key":"R4-20260430","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1212\/01.wnl.0000266628.43760.8c","article-title":"Impact of cognitive 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