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Skeletal muscle, a critical tissue for glucose and lipid metabolism, is especially vulnerable to prenatal environmental insults. However, the effects of intrauterine hyperglycemia (IUHG) on offspring skeletal muscle development remain poorly understood. This study aimed to investigate the effects of IUHG on skeletal muscle development in offspring and evaluate whether postnatal exercise could mitigate these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pregnant mice were assigned to GDM and control groups. Offspring were further divided into control and exercise subgroups. Body weight, glucose tolerance test (GTT), insulin tolerance test (ITT), body composition, muscle strength and exercise capacity were assessed. At 20\u2009weeks of age, skeletal muscle morphology was evaluated via various staining and Transmission Electron Microscope. Transcriptomic changes were analysed by RNA sequencing (RNA\u2010seq) and chromatin accessibility was assessed using ATAC\u2010seq to identify molecular mechanisms underlying IUHG\u2010induced alterations. Additionally, primary fetal myoblasts were cultured under normal and high\u2010glucose conditions to investigate metabolic changes and lipid accumulation in\u00a0vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Offspring exposed to IUHG exhibited increased body weight, impaired glucose and insulin tolerance, altered body composition, reduced muscle strength and diminished exercise capacity at adulthood. Exercise intervention in diabetic offspring improved the muscle ratio (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), fat ratio (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), lipid profiles (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.005) and muscle structure and strength (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.005). Transcriptomic and epigenomic profiling identified significant changes in genes and regulatory elements associated with immune regulation, myogenesis, lipid metabolism and inflammation in GDM\u2010exposed offspring. In\u00a0vitro, high\u2010glucose exposure of E14.5d fetal myoblasts led to significant metabolic reprogramming, including lipid accumulation and disruptions in glycolysis and oxidative metabolism. Furthermore, the expression of AP\u20101 family members Fos and Junb was up\u2010regulated in myoblasts under high\u2010glucose conditions, which aligns with the findings in the in\u00a0vivo models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IUHG disrupts skeletal muscle development and metabolic function in offspring through structural, transcriptional and epigenetic alterations. Postnatal exercise partially reversed these impairments, highlighting its potential as a non\u2010pharmacological intervention. These findings provide new insights into the developmental origins of skeletal muscle dysfunction in GDM\u2010exposed offspring and underscore the importance of early prevention strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70177","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:20:37Z","timestamp":1769145637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi\u2010Omics Revealed the Effects of Intrauterine Hyperglycemia Exposure on the Development of Skeletal Muscle in Offspring"],"prefix":"10.1002","volume":"17","author":[{"given":"Rui","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"},{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital Zhejiang University School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsen","family":"She","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"},{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital Zhejiang University School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishang","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital Zhejiang University School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Mo","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"},{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital Zhejiang University School of Medicine  Zhejiang 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