{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:25:25Z","timestamp":1768314325574,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:00:00Z","timestamp":1576627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2012CB124703"],"award-info":[{"award-number":["2012CB124703"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFD0500502"],"award-info":[{"award-number":["2016YFD0500502"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Sci Food Agric"],"published-print":{"date-parts":[[2020,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>We reported previously that maternal betaine promotes hepatic insulin\u2010like growth factor (IGF2) expression in F1 offspring rats through hypermethylation of the IGF2\/H19 imprinting control region (ICR). It remains unknown whether this acquired trait can be transmitted to the F2 generation. This study aimed to determine whether dietary betaine supplementation to grand dams affects the hepatic IGF2 expression in F2 rat offspring and how it is related to alterations in DNA methylation. F2 rat offspring derived from grand dams fed basal or betaine\u2010supplemented diet (10 g kg<jats:sup>\u22121<\/jats:sup>) were examined at weaning. Serum IGF2 concentration was measured with enzyme\u2010linked immunosorbent assay (ELISA). Hepatic expression of IGF2, together with other proliferation and apoptosis markers, was determined by using quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry. The methylation status of the <jats:italic>IGF2\/H19<\/jats:italic> ICR and the promoters of IGF2 gene were detected by methylated DNA immunoprecipitation quantitative polymerase chain reaction (MeDIP\u2010qPCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The maternal betaine\u2010induced up\u2010regulation of hepatic IGF2 expression in F1 rat offspring was transmitted to the F2 generation. The F2 rats from the betaine group demonstrated enhanced hepatic IGF2 expression at both mRNA and protein levels, in association with higher serum IGF2 concentration. No alterations were observed in the ICR methylation of the <jats:italic>IGF2\/H19<\/jats:italic> locus, and hypomethylation was detected in promoters of IGF2 gene in betaine group.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>These results indicate that maternal betaine enhances hepatic IGF2 expression in F2 rat offspring through modification of DNA methylation on IGF2 promoters. \u00a9 2019 Society of Chemical Industry<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsfa.10156","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T17:09:37Z","timestamp":1574442577000},"page":"1486-1494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Grandmaternal betaine supplementation enhances hepatic IGF2 expression in F2 rat offspring through modification of promoter DNA methylation"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6537-077X","authenticated-orcid":false,"given":"Shu","family":"Yang","sequence":"first","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health &amp; Food Safety Nanjing Agricultural University  Nanjing P. 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