Microorganisms in the human placenta are associated with altered CpG methylation of immune and inflammation-related genes

Microorganisms in the placenta have been linked to adverse pregnancy outcomes as well as neonatal illness. Inflammation in the placenta has been identified as a contributing factor in this association, but the underlying biological mechanisms are not yet fully understood. The placental epigenome may serve as an intermediate between placental microbes and inflammation, contributing to adverse outcomes in the offspring. In the present study, genome-wide DNA methylation (n = 486,428 CpG sites) of 84 placentas was analyzed in relation to 16 species of placental microorganisms using samples collected from the Extremely Low Gestation Age Newborns (ELGAN) cohort. A total of n = 1,789 CpG sites, corresponding to n = 1,079 genes, displayed differential methylation (q<0.1) in relation to microorganisms. The altered genes encode for proteins that are involved in immune/inflammatory responses, specifically the NF-κB signaling pathway. These data support bacteria-dependent epigenetic patterning in the placenta and provide potential insight into mechanisms that associate the presence of microorganisms in the placenta to pregnancy and neonatal outcomes. This study lays the foundation for investigations of the placental microbiome and its role in placental function.

• Publication year

  2017

• Venue

  PLoS ONE

• Publication date

  2017-12-14

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1371/journal.pone.0188664PMID 29240761PMCID 5730116
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The role of

  2020cited by this paper
• The NF-κB family: Key players during embryonic development and HSC emergence.

  2016cited by this paper
• A cross-study analysis of prenatal exposures to environmental contaminants and the epigenome: support for stress-responsive transcription factor occupancy as a mediator of gene-specific CpG methylation patterning

  2016cited by this paper
• Impact of SNPs on methylation readouts by Illumina Infinium HumanMethylation450 BeadChip Array: implications for comparative population studies

  2015cited by this paper
• IL-1,IL-6,IL-8与胃癌的关系

  2015cited by this paper
• Epigenetics and Preeclampsia: Defining Functional Epimutations in the Preeclamptic Placenta Related to the TGF-β Pathway

  2015influential reference
• Systems approach to the study of brain damage in the very preterm newborn

  2015cited by this paper
• Understanding the Complexity of the Immune System during Pregnancy

  2014cited by this paper
• The Placenta Harbors a Unique Microbiome

  2014cited by this paper
• A data-driven approach to preprocessing Illumina 450K methylation array data

  2013cited by this paper
• Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations.

  2013cited by this paper
• Molecular Pathways Molecular Pathways : Involvement of Helicobacter pylori – Triggered In fl ammation in the Formation of an Epigenetic Field Defect , and Its Usefulness as Cancer Risk and Exposure Markers

  2012cited by this paper
• Uropathogenic E. coli infection provokes epigenetic downregulation of CDKN2A (p16INK4A) in uroepithelial cells

  2011cited by this paper
• Maternal Microbe-Specific Modulation of Inflammatory Response in Extremely Low-Gestational-Age Newborns

  2011cited by this paper
• Understanding the role of growth factors in embryonic development: insights from the lens

  2011cited by this paper
• Regulated suppression of NF-κB throughout pregnancy maintains a favourable cytokine environment necessary for pregnancy success.

  2011cited by this paper
• Epigenetic regulation of human β-defensin 2 and CC chemokine ligand 20 expression in gingival epithelial cells in response to oral bacteria

  2011cited by this paper
• NF-kappaB function in the human myometrium during pregnancy and parturition.

  2010cited by this paper
• REVIEW ARTICLE: The Immune System in Pregnancy: A Unique Complexity

  2010cited by this paper
• Inflammatory Cytokines and Spontaneous Preterm Birth in Asymptomatic Women: A Systematic Review

  2010cited by this paper
• Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis.

  2010cited by this paper
• Transmission of Diverse Oral Bacteria to Murine Placenta: Evidence for the Oral Microbiome as a Potential Source of Intrauterine Infection

  2010cited by this paper
• Gene expression in the placenta: maternal stress and epigenetic responses.

  2010cited by this paper
• Microbe-induced epigenetic alterations in host cells: the coming era of patho-epigenetics of microbial infections. A review.

  2009cited by this paper
• The ELGAN study of the brain and related disorders in extremely low gestational age newborns.

  2009cited by this paper
• Detection of bacteria in placental tissues obtained from extremely low gestational age neonates.

  2008cited by this paper
• Colonization of second-trimester placenta parenchyma.

  2008cited by this paper
• The role and regulation of the nuclear factor kappa B signalling pathway in human labour.

  2007cited by this paper
• Bacterial Infection Promotes DNA Hypermethylation

  2007cited by this paper
• High Levels of Aberrant DNA Methylation in Helicobacter pylori–Infected Gastric Mucosae and its Possible Association with Gastric Cancer Risk

  2006cited by this paper
• Core transcriptional regulatory circuitry in human embryonic stem cells.

  2005cited by this paper
• The role of nuclear factor kappa B in human labour.

  2005cited by this paper
• Functions and regulations of fibroblast growth factor signaling during embryonic development.

  2005cited by this paper
• Faculty Opinions recommendation of De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling.

  2004cited by this paper
• De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling

  2004cited by this paper
• The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses

  2004cited by this paper
• Pregnancy-Specific Down-Regulation of NF-κB Expression in T Cells in Humans Is Essential for the Maintenance of the Cytokine Profile Required for Pregnancy Success1

  2004cited by this paper
• Missing pieces in the NF-kappaB puzzle.

  2002cited by this paper
• The role of the placenta in fetal programming-a review.

  2002cited by this paper
• The American Society for Microbiology.

  2001cited by this paper
• Production of Pro- and Anti-Inflammatory Cytokines of Human Placental Trophoblasts in Response to Pathogenic Bacteria

  2001cited by this paper
• Targeted Disruption of the ζPKC Gene Results in the Impairment of the NF-κB Pathway

  2001cited by this paper
• Targeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway.

  2001cited by this paper
• Intrauterine infection and preterm delivery.

  2000influential reference
• Role of transcription factors in fetal lung development and surfactant protein gene expression.

  2000cited by this paper
• TNF, IL-1, IL-6, IL-8 and soluble TNF receptors in relation to chorioamnionitis and premature labor

  1998cited by this paper
• Macrophages ingest and are activated by bacterial DNA.

  1996cited by this paper
• The NF-kappa B and I kappa B proteins: new discoveries and insights.

  1996cited by this paper
• THE NF-κB AND IκB PROTEINS: New Discoveries and Insights

  1996cited by this paper
• zeta PKC induces phosphorylation and inactivation of I kappa B‐alpha in vitro.

  1994cited by this paper
• CpG-rich islands and the function of DNA methylation

  1986cited by this paper
• Manual of Clinical Microbiology

  1970cited by this paper

• Cross‐Tissue Specificity of Pediatric DNA Methylation Associated With Cumulative Family Stress

  2025cites this paper
• Evaluating the association between placenta DNA methylation and cognitive functions in the offspring

  2024cites this paper
• Guardians under Siege: Exploring Pollution’s Effects on Human Immunity

  2024cites this paper
• Cross-Tissue Specificity of Pediatric DNA Methylation Associated with Cumulative Family Adversity

  2023cites this paper
• Platelet-to-Lymphocyte Ratio (PLR) as the Prognostic Factor for Recurrence/Residual Disease in HSIL Patients After LEEP

  2023cites this paper
• Extreme prematurity: Risk and resiliency.

  2022cites this paper
• The placenta epigenome-brain axis: placental epigenomic and transcriptomic responses that preprogram cognitive impairment.

  2022cites this paper
• Environmental influences on child health outcomes: cohorts of individuals born very preterm

  2022cites this paper
• Identification of Microorganisms associated with intraamniotic infection among women with preterm birth at Ruhengeri Referral Hospital, Rwanda: A case control study

  2021cites this paper
• Metagenomic profiling of placental tissue suggests DNA virus infection of the placenta is rare

  2021cites this paper
• Racial and ethnic representation in epigenomic studies of preterm birth: a systematic review.

  2020cites this paper
• The emerging role of epigenetics in the immune response to vaccination and infection: a systematic review

  2020cites this paper
• Modulation of Placental Gene Expression in Small-for-Gestational-Age Infants

  2020cites this paper
• Genetic and epigenetic factors and early life inflammation as predictors of neurodevelopmental outcomes.

  2020cites this paper
• Placental programming, perinatal inflammation, and neurodevelopment impairment among those born extremely preterm

  2020cites this paper
• Comparative analysis of immune related genes between domestic pig and germ-free minipig

  2020cites this paper
• G ENETIC AND E PIGENETIC F ACTORS AND E ARLY L IFE I NFLAMMATION AS P REDICTORS OF N EURODEVELOPMENTAL O UTCOMES

  2020cites this paper
• Lymphocytes T Helper 17 in Multiple Sclerosis: Regulation by Intestinal Microbiota

  2019cites this paper
• A review of maternal prenatal exposures to environmental chemicals and psychosocial stressors—implications for research on perinatal outcomes in the ECHO program

  2019cites this paper
• Bacterial Colonization of the Female Upper Genital Tract

  2019cites this paper
• Microorganisms in the Placenta: Links to Early-Life Inflammation and Neurodevelopment in Children

  2019cites this paper
• Intrauterine Microbiota: Missing, or the Missing Link?

  2019cites this paper
• Sleep Apnoea and Early Antecedents of Adult Disease

  2018cites this paper
• Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity

  2018cites this paper