{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:47:54Z","timestamp":1793850474374,"version":"4.6.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K17891"],"award-info":[{"award-number":["21K17891"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008731","name":"Nakatomi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genomics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Mitochondria have their own circular multi-copy genome (mtDNA), and abnormalities in the copy number are implicated in mitochondrial dysfunction, which contributes to a variety of aging-related pathologies. However, not much is known about the genetic correlation of mtDNA copy number across multiple generations and its physiological significance.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We measured the mtDNA copy number in cord blood or peripheral blood from 149 three-generation families, specifically the newborns, parents, and grandparents, of 149 families, totaling 1041 individuals. All of the biological specimens and information were provided by the Tohoku Medical Megabank Project in Japan. We also analyzed their maternal factors during pregnancy and neonatal outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>While the maternal peripheral blood mtDNA copy number was lower than that of other adult family members, it was negatively correlated with cord blood mtDNA copy number in male infants. Also, cord blood mtDNA copy numbers were negatively correlated with perinatal outcomes, such as gestation age, birth weight, and umbilical cord length, for both male and female neonates. Furthermore, the mtDNA copy number in the infants born to mothers who took folic acid supplements during pregnancy would be lower than in the infants born to mothers who did not take them.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This data-driven study offers the most comprehensive view to date on the genetic and physiological significance of mtDNA copy number in cord blood or peripheral blood taken from three generations, totaling more than 1000 individuals. Our findings indicate that mtDNA copy number would be one of the transgenerational biomarkers for assessing perinatal outcomes, as well as that appropriate medical interventions could improve the outcomes via quantitative changes in mtDNA.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40246-023-00567-4","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T03:02:18Z","timestamp":1702609338000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mitochondrial DNA copy number variation across three generations: a possible biomarker for assessing perinatal outcomes"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-187X","authenticated-orcid":false,"given":"Hisanori","family":"Fukunaga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"567_CR1","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1172\/JCI61398","volume":"123","author":"DC Wallace","year":"2013","unstructured":"Wallace DC. A mitochondrial bioenergetic etiology of disease. J Clin Invest. 2013;123:1405\u201312.","journal-title":"J Clin Invest"},{"key":"567_CR2","doi-asserted-by":"publisher","first-page":"6634","DOI":"10.3390\/ijms22126634","volume":"22","author":"H Fukunaga","year":"2021","unstructured":"Fukunaga H, Mitochondrial DNA. Copy number and developmental origins of health and disease (DOHaD). Int J Mol Sci. 2021;22:6634.","journal-title":"Int J Mol Sci"},{"key":"567_CR3","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1007\/s00439-014-1458-9","volume":"133","author":"J Mengel-From","year":"2014","unstructured":"Mengel-From J, Thinggaard M, Dalg\u00e5rd C, Kyvik KO, Christensen K, Christiansen L. Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly. 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Breast Cancer Res. 2018;20:29.","journal-title":"Breast Cancer Res"},{"key":"567_CR6","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.kint.2019.04.021","volume":"96","author":"F Fazzini","year":"2019","unstructured":"Fazzini F, Lamina C, Fendt L, Schultheiss UT, Kotsis F, Hicks AA, et al. Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease. Kidney Int. 2019;96:480\u20138.","journal-title":"Kidney Int"},{"key":"567_CR7","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s13073-020-00778-7","volume":"12","author":"CA Castellani","year":"2020","unstructured":"Castellani CA, Longchamps RJ, Sumpter JA, Newcomb CE, Lane JA, Grove ML, et al. Mitochondrial DNA copy number can influence mortality and cardiovascular disease via methylation of nuclear DNA CpGs. 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Methods Mol Biol. 2015;1241:23\u201338.","journal-title":"Methods Mol Biol"}],"container-title":["Human Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-023-00567-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40246-023-00567-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-023-00567-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T03:04:29Z","timestamp":1702609469000},"score":1,"resource":{"primary":{"URL":"https:\/\/humgenomics.biomedcentral.com\/articles\/10.1186\/s40246-023-00567-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["567"],"URL":"https:\/\/doi.org\/10.1186\/s40246-023-00567-4","relation":{},"ISSN":["1479-7364"],"issn-type":[{"value":"1479-7364","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]},"assertion":[{"value":"28 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The current study is conformed to the principles of the Helsinki Declaration. Ethical approval for this study was obtained from the Ethical Review Committee of our institution (reference no. Kanken 22-140). Also, this study was approved by the Sample and Data Access Committee of ToMMo and IMM (reference no. 2021-0021-1).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"113"}}