Pregestational diabetes alters cardiac structure and function of neonatal rats through developmental plasticity
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 sever...
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Published in | Frontiers in cardiovascular medicine Vol. 9; p. 919293 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
13.09.2022
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Amaresh Ranjan, Midwestern University, United States; Fiona Lewis-McDougall, Queen Mary University of London, United Kingdom; Shizuka Uchida, Aalborg University Copenhagen, Denmark; Sneha Mishra, Aarhus University, Denmark These authors have contributed equally to this work Edited by: N. Ravi Sundaresan, Indian Institute of Science (IISc), India This article was submitted to Cardiovascular Metabolism, a section of the journal Frontiers in Cardiovascular Medicine |
ISSN: | 2297-055X 2297-055X |
DOI: | 10.3389/fcvm.2022.919293 |