{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:47:44Z","timestamp":1785422864625,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273747"],"award-info":[{"award-number":["82273747"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82273747"],"award-info":[{"award-number":["82273747"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Chongqing Graduate Research Innovation Project","award":["CYB240297"],"award-info":[{"award-number":["CYB240297"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2702900"],"award-info":[{"award-number":["2022YFC2702900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Circadian disruption has been linked to impaired male fecundity, but its association with semen molecular phenotypes and circadian genes remains unclear. We analyzed 441 men from the Male Reproductive Health in Chongqing College Students cohort to assess whether social jetlag, an indicator of circadian disruption, was associated with whole-semen mitochondrial DNA copy number (mtDNAcn), an emerging biomarker of male fecundity. Core circadian genes related to mtDNAcn were screened using genetic polymorphism data. A light-cycle phase-shifting mouse model, Cry1-knockout mice, and testicular Cry1 re-expression models were used for experimental validation, with histology, transcriptomics, single-cell data, and proteomics analyses used to explore mechanisms. Social jetlag was associated with higher mtDNAcn in men (1.29-fold, p = 0.026), with a concordant increase in circadian-disrupted mice (1.33-fold, p = 0.010). Among core circadian genes, CRY1 showed the strongest association with mtDNAcn (p = 0.048). Cry1 knockout elevated mtDNAcn (2.18-fold, p &lt; 0.001), whereas testicular Cry1 re-expression reduced it toward wild-type levels. Circadian disruption and Cry1 deficiency were accompanied by seminiferous epithelial disorganization, spermatogenesis-related transcriptomic changes, and altered mitochondrial pathway signatures. To our knowledge, this study is the first to identify whole-semen mtDNAcn as a circadian-disruption-associated molecular phenotype and supports CRY1 as a candidate regulator.<\/jats:p>","DOI":"10.3390\/ijms27156569","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"6569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circadian Disruption Is Associated with Elevated Whole-Semen mtDNA Copy Number and Implicates CRY1 as a Candidate Regulator in Humans and Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9134-0722","authenticated-orcid":false,"given":"Mengchao","family":"He","sequence":"first","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimeng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhong","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojian","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Rhythm and Metabolism, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/ejn.14255","article-title":"Circadian Disruption: What Do We Actually Mean?","volume":"51","author":"Vetter","year":"2018","journal-title":"Eur. 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