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Open AccessArticle

Multi-Omics Integration Reveals Short and Long-Term Effects of Gestational Hypoxia on the Heart Development

Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA
Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
Authors to whom correspondence should be addressed.
Cells 2019, 8(12), 1608;
Received: 1 November 2019 / Revised: 9 December 2019 / Accepted: 10 December 2019 / Published: 11 December 2019
(This article belongs to the Collection Regulatory Functions of microRNAs)
Antenatal hypoxia caused epigenetic reprogramming of methylome and transcriptome in the developing heart and increased the risk of heart disease later in life. Herein, we investigated the impact of gestational hypoxia in proteome and metabolome in the hearts of fetus and adult offspring. Pregnant rats were treated with normoxia or hypoxia (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from near-term fetuses and 5 month-old offspring, and proteomics and metabolomics profiling was determined. The data demonstrated that antenatal hypoxia altered proteomics and metabolomics profiling in the heart, impacting energy metabolism, lipid metabolism, oxidative stress, and inflammation-related pathways in a developmental and sex dependent manner. Of importance, integrating multi-omics data of transcriptomics, proteomics, and metabolomics profiling revealed reprogramming of the mitochondrion, especially in two clusters: (a) the cluster associated with “mitochondrial translation”/“aminoacyl t-RNA biosynthesis”/“one-carbon pool of folate”/“DNA methylation”; and (b) the cluster with “mitochondrion”/“TCA cycle and respiratory electron transfer”/“acyl-CoA dehydrogenase”/“oxidative phosphorylation”/“complex I”/“troponin myosin cardiac complex”. Our study provides a powerful means of multi-omics data integration and reveals new insights into phenotypic reprogramming of the mitochondrion in the developing heart by fetal hypoxia, contributing to an increase in the heart vulnerability to disease later in life. View Full-Text
Keywords: hypoxia; heart; proteome; metabolome; multi-omics integration hypoxia; heart; proteome; metabolome; multi-omics integration
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Gao, Y.; Dasgupta, C.; Huang, L.; Song, R.; Zhang, Z.; Zhang, L. Multi-Omics Integration Reveals Short and Long-Term Effects of Gestational Hypoxia on the Heart Development. Cells 2019, 8, 1608.

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