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Exploring the Association of Maternal Covid-19 Infection and Epigenetic Regulation of Metabolic Pathways in Newborn Children
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- Author / Creator
- Nezarat, Fatemeh
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Abstract
Background: SARS-CoV-2 infection during pregnancy has emerged as a significant concern due to its potential implications for fetal health. Viral infections can induce inflammatory responses and immune activation in pregnant individuals, which may harm the developing fetus through epigenetic alterations, potentially influencing gene expression patterns and developmental trajectories even without vertical transmission. While much remains to be understood about the specific effects of SARS-CoV-2 on pregnancy, previous research on other viral infections, such as influenza, Zika virus, and cytomegalovirus, has highlighted the potential for adverse outcomes, including asthma, metabolic disease, and mental illness.
Methods: We used a gene expression dataset accessed on the Gene Expression Omnibus database (GSE 165193), including 14,748 cells from cases, and 11,222 cells from controls. In this case-control study, droplet-based single-cell RNA-sequencing (SC-RNA Seq) and T-cell receptor sequencing were performed on Cord Blood Mononuclear Cells (CBMCs) involving three-term gestation infants (>37 weeks) born to mothers with mild COVID-19 symptoms (cases) and three infants born to uninfected mothers (controls). Initially the differential expression of the "ReactomeEpigeneticRegulationofGene_Expression" collection was evaluated employing the linear combination test (LCT) on 25,970 cells including 18 types to discern epigenetic modulation comparing cases vs. controls. Subsequently, differential expression of biological pathway collection of Kyoto Encyclopedia of Genes and Genomes (KEGG) in CBMCs of COVID-19-infected mothers exhibiting epigenetic modulation explored by performing Linear Combination Test (LCT).
Results: Our analysis revealed differential expression of genes associated with epigenetic regulation in specific cell types of cord blood from infants born to COVID-19-infected mothers compared to controls. Subsequent analysis using KEGG collections on SARS-CoV-2 infected samples identified disturbed biological pathways related to amino acid and lipid biosynthesis and metabolism. These pathways have previously been implicated in metabolic diseases, particularly cardiovascular disease.
Conclusions: Maternal COVID-19 infection during pregnancy is associated with epigenetic modulation compared to healthy pregnant mothers. The identification of disturbed biological pathways in COVID-19-infected mothers suggests a link between maternal infection, epigenetic modulation, and the development of metabolic diseases in offspring. These findings underscore the importance of prenatal care and highlight potential targets for preventive interventions to mitigate long-term metabolic disease risk, specifically cardiovascular diseases (CVD) in neonates born to COVID-19-infected-mothers. -
- Subjects / Keywords
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- Graduation date
- Fall 2024
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.