Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity
| Autor: | Peter W. Nathanielsz, Alina Maloyan, Mark J. Nijland, Steven Huffman, Leslie Myatt, Laura A. Cox, Sribalasubashini Muralimanoharan |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Physiology Offspring Mothers Disease Biology Diet High-Fat Bioinformatics Fetus Downregulation and upregulation Internal medicine microRNA Genetics medicine Animals Cluster Analysis Humans Obesity Epigenetics Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis RNA Gene Expression Profiling Myocardium Gene Expression Regulation Developmental Reproducibility of Results Heart Non-coding RNA Gene expression profiling MicroRNAs Phenotype Endocrinology Female Papio |
| Zdroj: | Physiological Genomics. 45:889-900 |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00050.2013 |
| Popis: | Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD. |
| Databáze: | OpenAIRE |
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