DNA Methylation Profile in Human Cord Blood Mononuclear Leukocytes From Term Neonates: Effects of Histological Chorioamnionitis

Fong, Gina; Betal, Suhita Gayen; Murthy, Swati; Favara, Michael; Chan, Joanna; Addya, Sankar; Shaffer, Thomas H.; Greenspan, Jay S.; Bhandari, Vineet; Li, Dongmei; Rahman, Irfan; Aghai, Zubair H.

doi:10.3389/fped.2020.00437

Cited by 9 publications

(9 citation statements)

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“…The details of study design, informed consents, UCB sample collection, processing, storage, DNA isolation and global DNA methylation analysis is described elsewhere. 14,18 In brief, UCB samples were collected from 8 infants exposed to COVID-19 infection during pregnancy and 8 control infants. The genome-wide DNA methylation study was performed using the Illumina Methylation EPIC Array (cat# WG-317-1001, Illumina Inc., San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

“…16,17 DNA methylation is one mechanism by which this change may occur. 18 It is an enzyme-mediated change during which a methyl group is added to cytosine at specific sites that leads to transcriptional regulation. 19 Intrauterine infections, such as histologic chorioamnionitis, have been associated with epigenetic changes via DNA methylation of neonatal genes.…”

Section: Introductionmentioning

confidence: 99%

“…19 Intrauterine infections, such as histologic chorioamnionitis, have been associated with epigenetic changes via DNA methylation of neonatal genes. 18,20 Exposure to COVID-19 during pregnancy is likely to have a similar effect in the perinatal environment that could lead to alteration in fetal DNA methylation. We hypothesized that early epigenetic signatures of COVID-19 exposure during pregnancy are detectable in UCB cells.…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates

et al. 2023

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Background: The global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 18.4% of total Covid-19 cases were reported in children. Even though vertical transmission from mother to infant is likely to occur at a low rate, exposure to COVID-19 during fetal life may alter DNA methylation patterns with potential long-term effects. Objective: To determine if COVID-19 infection during pregnancy alters the DNA methylation patterns in umbilical cord blood cells from term infants and to identify potential pathways and genes affected by exposure to COVID-19 infection. Methods: Umbilical cord blood was collected from 8 infants exposed to COVID-19 during pregnancy and 8 control infants with no COVID-19 exposure. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC Array. Results: 119 differentially methylated loci were identified at the FDR level of 0.20 (64 hypermethylated loci and 55 hypomethylated loci) in umbilical cord blood cells of COVID-19 exposed neonates compared to the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to stress response (corticotropin releasing hormone signaling, glucocorticoid receptor signaling, and oxytocin in brain signaling pathway), and cardiovascular disease and development (nitric oxide signaling in the cardiovascular system, apelin cardiomyocyte signaling pathways, factors promoting cardiogenesis, and renin-angiotensin signaling). The genes affected by the differential methylations were associated with cardiac, renal, hepatic, neurological diseases, developmental and immunological disorders. Conclusions: COVID-19 induces differential DNA methylation in umbilical cord blood cells. The differentially methylated genes may contribute to hepatic, renal, cardiac, developmental and immunological disorders in offspring born to mothers with COVID-19 infection during pregnancy, and their developmental regulation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates

et al. 2023

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“…DNA methylation patterns in chorionic villi, amnion, and chorion of CA and non-CA patients [ 244 , 252 ] showed DNA methylation sites close to the promoter regions of immune-response genes such as HLA-E, CXCL4, RAB27A, IRX2 , and HSD11B2 . In neonatal monocytes, the promoters of innate-immunity genes IL1B, IL6, IL12B, TNF , and CCR2 exhibit significantly higher histone-methylation modifications [ 253 , 254 ]. These monocytes under CA conditions express significantly lower levels of pro-inflammatory cytokines IL-1β, IL-6, IL-8 that might predispose the fetus to sepsis upon secondary infections [ 72 ].…”

Section: Pathogens As Epigenetic Modifiersmentioning

confidence: 99%

Role of Maternal Infections and Inflammatory Responses on Craniofacial Development

Bhagirath

Medapati

Jesus

et al. 2021

Front. Oral. Health

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Pregnancy is a tightly regulated immunological state. Mild environmental perturbations can affect the developing fetus significantly. Infections can elicit severe immunological cascades in the mother's body as well as the developing fetus. Maternal infections and resulting inflammatory responses can mediate epigenetic changes in the fetal genome, depending on the developmental stage. The craniofacial development begins at the early stages of embryogenesis. In this review, we will discuss the immunology of pregnancy and its responsive mechanisms on maternal infections. Further, we will also discuss the epigenetic effects of pathogens, their metabolites and resulting inflammatory responses on the fetus with a special focus on craniofacial development. Understanding the pathophysiological mechanisms of infections and dysregulated inflammatory responses during prenatal development could provide better insights into the origins of craniofacial birth defects.

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“…The fetal environment has been shown to impact neonatal gene expression with long-term consequences into childhood and even adult life ( 18 – 20 ). One mode for this environmental impact has been attributed to epigenetic modifications that lead to differential gene expression and can increase the risk for various immunological, allergic, and chronic diseases later in life ( 18 , 19 , 21 ). We have previously demonstrated fetal epigenetic changes in relation to maternal chorioamnionitis and given the known inflammatory effects of COVID-19 on maternal physiology ( 22 ), the fetal environment may also be altered with downstream effects on gene expression.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 Infection During Pregnancy Induces Differential Gene Expression in Human Cord Blood Cells From Term Neonates

et al. 2022

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BackgroundThe COVID-19 pandemic continues worldwide with fluctuating case numbers in the United States. This pandemic has affected every segment of the population with more recent hospitalizations in the pediatric population. Vertical transmission of COVID-19 is uncommon, but reports show that there are thrombotic, vascular, and inflammatory changes in the placenta to which neonates are prenatally exposed. Individuals exposed in utero to influenza during the 1918 pandemic had increased risk for heart disease, kidney disease, diabetes, stomach disease and hypertension. Early exposure of COVID-19 during fetal life may lead to altered gene expression with potential long-term consequences.ObjectiveTo determine if gene expression is altered in cord blood cells from term neonates who were exposed to COVID-19 during pregnancy and to identify potential gene pathways impacted by maternal COVID-19.MethodsCord blood was collected from 16 term neonates (8 exposed to COVID-19 during pregnancy and 8 controls without exposure to COVID-19). Genome-wide gene expression screening was performed using Human Clariom S gene chips on total RNA extracted from cord blood cells.ResultsWe identified 510 differentially expressed genes (374 genes up-regulated, 136 genes down-regulated, fold change ≥1.5, p-value ≤ 0.05) in cord blood cells associated with exposure to COVID-19 during pregnancy. Ingenuity Pathway Analysis identified important canonical pathways associated with diseases such as cardiovascular disease, hematological disease, embryonic cancer and cellular development. Tox functions related to cardiotoxicity, hepatotoxicity and nephrotoxicity were also altered after exposure to COVID-19 during pregnancy.ConclusionsExposure to COVID-19 during pregnancy induces differential gene expression in cord blood cells. The differentially expressed genes may potentially contribute to cardiac, hepatic, renal and immunological disorders in offspring exposed to COVID-19 during pregnancy. These findings lead to a further understanding of the effects of COVID-19 exposure at an early stage of life and its potential long-term consequences as well as therapeutic targets.

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DNA Methylation Profile in Human Cord Blood Mononuclear Leukocytes From Term Neonates: Effects of Histological Chorioamnionitis

Cited by 9 publications

References 44 publications

SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates

SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates

Role of Maternal Infections and Inflammatory Responses on Craniofacial Development

COVID-19 Infection During Pregnancy Induces Differential Gene Expression in Human Cord Blood Cells From Term Neonates

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