{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:28:04Z","timestamp":1779377284778,"version":"3.53.1"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"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":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Maternal obesity (MO) impairs fetal skeletal muscle development, but the underlying mechanisms remain poorly defined. The regulatory roles of lncRNA\n H19<\/jats:italic>\n and its first exon derived\n microRNA675<\/jats:italic>\n (\n miR675<\/jats:italic>\n ) in prenatal muscle development remain to be examined.\n H19<\/jats:italic>\n \/\n Igf2<\/jats:italic>\n are in the same imprinting cluster with\n H19<\/jats:italic>\n expressed from the maternal allele while\n Igf2<\/jats:italic>\n expresses paternally.\n H19<\/jats:italic>\n contains a G\u2010rich loop, and KH\u2010type splicing regulatory protein (KHSRP) mediates the biogenesis of pre\u2010\n miRNAs<\/jats:italic>\n containing G\u2010rich loops, which depends on its phosphorylation by AKT, a key mediator of IGF2 signalling. This study aims to depict the elusive function of these regulators that are affected by MO during embryonic myogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Single\u2010cell transcriptomic sequencing and GeoMx spatial RNA sequencing were performed to identify the differentially expressed genes between embryos from MO and control (CT) mice. Both E11.5 and E13.5 embryos were collected and analysed to validate the sequencing data. The roles of\n H19<\/jats:italic>\n and\n miR657<\/jats:italic>\n in myogenesis were further analysed in P19 embryonic cells via CRISPR\/dCas9\u2010mediated\n H19<\/jats:italic>\n activation and inhibition. The epigenetic changes of\n H19<\/jats:italic>\n were analysed by methylated DNA immunoprecipitation, and allele\u2010targeted analysis of\n H19<\/jats:italic>\n was performed by crossing C57BL\/6J and CAST\/EiJ mice.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Transcriptomic analysis showed that MO embryos contained less differentiated myocytes (1.34%) than CT embryos (2.86%). Myogenesis\u2010related GO biological processes were down\u2010regulated in the MO embryonic myotome region. MO embryos showed lower expression of myogenic transcription factors such as\n Myf5<\/jats:italic>\n ,\n Myod1<\/jats:italic>\n ,\n Myog<\/jats:italic>\n ,\n Mef2c<\/jats:italic>\n and\n Myh3<\/jats:italic>\n (\n p<\/jats:italic>\n \u2009<\u20090.05). MO altered epigenetic modifications of the\n H19<\/jats:italic>\n genomic cluster, showing a decreased methylation level in\n H19<\/jats:italic>\n imprinting control region (\n p\u2009<<\/jats:italic>\n \u20090.05) and a diallelic expression pattern of\n H19<\/jats:italic>\n , which elevated its expression in MO embryos. Overexpression of\n H19<\/jats:italic>\n inhibited myogenesis in P19 cells, but\n miR675<\/jats:italic>\n promoted myogenesis, suggesting the critical regulatory roles of bioconversion of\n H19<\/jats:italic>\n to\n miR675<\/jats:italic>\n . A KHSRP mediates the biogenesis of\n miR675<\/jats:italic>\n , a process that relies on its phosphorylation by IGF2\/AKT signalling. Knocking\u2010down of KHSRP and inhibition of AKT abolished\n miR675<\/jats:italic>\n biogenesis. MO suppressed IGF2\/AKT signalling and blocked KHSRP\u2010dependent\n miR675<\/jats:italic>\n biogenesis in embryos.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We found differential effects of\n H19<\/jats:italic>\n and\n miR675<\/jats:italic>\n on embryonic myogenesis. MO up\u2010regulates\n H19<\/jats:italic>\n but blocks its\n miR675<\/jats:italic>\n bioconversion via suppressing IGF2\/AKT\/KHSRP signalling axis. Myogenesis in MO embryos was impeded due to the highly accumulated\n H19<\/jats:italic>\n and blocked\n miR675<\/jats:italic>\n biogenesis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13791","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T07:01:04Z","timestamp":1743490864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Balancing LncRNA H19 and miR\u2010675 Bioconversion as a Key Regulator of Embryonic Myogenesis Under Maternal Obesity"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1957-7232","authenticated-orcid":false,"given":"Yao","family":"Gao","sequence":"first","affiliation":[{"name":"Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences Washington State University Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md\u00a0Nazmul","family":"Hossain","sequence":"additional","affiliation":[{"name":"Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences Washington State University Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Nanjing Agricultural University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Nanjing Agricultural University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanene\u00a0Marie","family":"Deavila","sequence":"additional","affiliation":[{"name":"Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences Washington State University Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei\u2010Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Food Science Washington State University Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon\u00a0K.","family":"Murdoch","sequence":"additional","affiliation":[{"name":"Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences Washington State University Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7232-072X","authenticated-orcid":false,"given":"Min","family":"Du","sequence":"additional","affiliation":[{"name":"Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences Washington State University Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1","article-title":"Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017\u20102018","author":"Hales C. 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