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Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity.
- Source :
-
Physiological genomics [Physiol Genomics] 2013 Oct 01; Vol. 45 (19), pp. 889-900. Date of Electronic Publication: 2013 Aug 06. - Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- Animals
Cell Proliferation
Cluster Analysis
Diet, High-Fat
Female
Fetus pathology
Gene Expression Profiling
Gene Expression Regulation, Developmental
Humans
MicroRNAs metabolism
Myocardium pathology
Papio
Phenotype
Reproducibility of Results
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, RNA
Fetus metabolism
Heart embryology
MicroRNAs genetics
Mothers
Myocardium metabolism
Obesity metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1531-2267
- Volume :
- 45
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Physiological genomics
- Publication Type :
- Academic Journal
- Accession number :
- 23922128
- Full Text :
- https://doi.org/10.1152/physiolgenomics.00050.2013