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Med."],"abstract":"<jats:p>Pregestational diabetes (PGDM) leads to developmental impairment, especially cardiac dysfunction, in their offspring. The hyperglycemic microenvironment inside the uterus alters the cardiac plasticity characterized by electrical and structural remodeling of the heart. The altered expression of several transcription factors due to hyperglycemia during fetal development might be responsible for molecular defects and phenotypic changes in the heart. The molecular mechanism of the developmental defects in the heart due to PGDM remains unclear. To understand the molecular defects in the 2-days old neonatal rats, streptozotocin-induced diabetic female rats were bred with healthy male rats. We collected 2-day-old hearts from the neonates and identified the molecular basis for phenotypic changes. Neonates from diabetic mothers showed altered electrocardiography and echocardiography parameters. Transcriptomic profiling of the RNA-seq data revealed that several altered genes were associated with heart development, myocardial fibrosis, cardiac conduction, and cell proliferation. Histopathology data showed the presence of focal cardiac fibrosis and increased cell proliferation in neonates from diabetic mothers. Thus, our results provide a comprehensive map of the cellular events and molecular pathways perturbed in the neonatal heart during PGDM. All of the molecular and structural changes lead to developmental plasticity in neonatal rat hearts and develop cardiac anomalies in their early life.<\/jats:p>","DOI":"10.3389\/fcvm.2022.919293","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T13:15:33Z","timestamp":1663074933000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Pregestational diabetes alters cardiac structure and function of neonatal rats through developmental plasticity"],"prefix":"10.3389","volume":"9","author":[{"given":"Md Jahangir","family":"Alam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shravan Kumar","family":"Uppulapu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Tiwari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bincy","family":"Varghese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheb Anwar","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramu","family":"Adela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudheer Kumar","family":"Arava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay K.","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"624939","DOI":"10.1155\/2014\/624939","article-title":"Cardiomyopathy in offspring of pregestational diabetic mouse pregnancy.","volume":"2014","author":"Dowling","year":"2014","journal-title":"J Diabetes Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s11845-011-0682-8","article-title":"Pregnancy in women with type 1 and type 2 diabetes in Dublin.","volume":"180","author":"Higgins","year":"2011","journal-title":"Ir J Med Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1111\/j.1464-5491.2008.02431.x","article-title":"Outcomes of pregnancies in women with pre-gestational diabetes mellitus and gestational diabetes mellitus; a population-based study in New South Wales, Australia, 1998-2002.","volume":"25","author":"Shand","year":"2008","journal-title":"Diabet Med J Br Diabet Assoc."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.3109\/00016349.2010.518594","article-title":"Congenital anomalies in newborns of women with type 1 diabetes: nationwide population-based study in Norway, 1999-2004.","volume":"89","author":"Eidem","year":"2010","journal-title":"Acta Obstet Gynecol Scand."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1007\/s00125-011-2281-7","article-title":"Perinatal and infant mortality in term and preterm births among women with type 1 diabetes.","volume":"54","author":"Eidem","year":"2011","journal-title":"Diabetologia."},{"key":"B6","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1136\/bmj.38856.692986.AE","article-title":"Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study.","volume":"333","author":"Macintosh","year":"2006","journal-title":"BMJ."},{"key":"B7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00059-010-3244-3","article-title":"Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. 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