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Microorganisms in the human placenta are associated with altered CpG methylation of immune and inflammation-related
Martha Scott Tomlinson1, Paige A Bommarito1, Elizabeth M Martin1
1Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Abstract:
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.
Insights
Placental microbes alter DNA methylation patterns, influencing genes involved in inflammation and potentially impacting pregnancy outcomes. This epigenetic link sheds light on how the placental microbiome affects maternal and infant health.
Area of Science:
- Reproductive biology
- Epigenetics
- Microbiome research
Background:
- Placental microorganisms are associated with adverse pregnancy and neonatal outcomes.
- Inflammation is a key factor, but its link to microbes is not fully understood.
- The placental epigenome may mediate the effects of microbes on inflammation.
Purpose of the Study:
- To investigate genome-wide DNA methylation in placentas related to microbial presence.
- To identify genes and pathways affected by microbial-associated epigenetic changes.
- To explore the role of the placental epigenome in mediating microbial impacts.
Main Methods:
- Genome-wide DNA methylation analysis of 486,428 CpG sites in 84 placentas.
- Correlation analysis between methylation data and 16 species of placental microorganisms.
- Utilized samples from the Extremely Low Gestation Age Newborns (ELGAN) cohort.
Main Results:
- Identified 1,789 differentially methylated CpG sites (q<0.1) linked to microorganisms, corresponding to 1,079 genes.
- Enriched genes are involved in immune and inflammatory responses, notably the NF-κB signaling pathway.
- Demonstrated bacteria-dependent epigenetic patterning in the placenta.
Conclusions:
- Microbial presence in the placenta is associated with significant alterations in DNA methylation.
- Epigenetic modifications in the placenta may link microbial exposure to inflammatory pathways.
- Findings provide a foundation for understanding the placental microbiome's role in pregnancy and neonatal health.
