Maternal Inflammation Alters Nuclear and Mitochondrial DNA Methylation Patterns in Neonatal Brain Monocytes.

Overview

1. Division of Neurology, Nemours Children’s Hospital, Wilmington, DE 19803, USA; (A.T.E.); (B.H.); (A.H.)
2. Division of Biomedical Research, Nemours Children’s Health, Wilmington, DE 19803, USA; (J.R.H.); (R.A.)
3. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
4. Medical and Molecular Sciences, University of Delaware, Newark, DE 19707, USA
5. Delaware Data Science Institute, Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE 19716, USA
6. School of Marine Science and Policy, University of Delaware, Newark, DE 19107, USA
7. Psychological and Brain Sciences, University of Delaware, Newark, DE 19107, USA

Abstract

Highlights: What are the main findings?

Widespread DNA methylation changes occur in brain monocytes of newborn mice after exposure to maternal immune activation in utero.

Mitochondrial DNA is hypermethylated in offspring’s brain monocytes after exposure to maternal immune activation in utero.

Nuclear genes are predominantly hypermethylated after maternal immune activation, and gene ontology analysis reveals these genes are important for neurodevelopment, immune response, and structural development.

What are the implications of the main findings?

Altered methylation of nuclear and mitochondrial DNA in brain monocytes may increase neurodevelopmental risk in offspring after maternal immune activation in utero.

Abstract: Neonatal hypoxic ischemic encephalopathy (HIE) is a common birth complication that can cause death or lifelong disabling conditions like cerebral palsy, epilepsy, and autism. It is well established that maternal infection and inflammation are significant risk factors for HIE but reasons for this increase in neurological risk to the offspring remain unknown. Inflammation or infection are associated with epigenetic changes and may contribute to the increased risk of neurodevelopmental disability in exposed offspring. Here, we analyzed and compared DNA methylation patterns in brain monocytes isolated from control, maternal immune activation (MIA), and an inflammation sensitized HIE (IS-HIE) CF-1 mouse model at postnatal day 7. We found that maternal inflammation induced significant methylation differences in neonates relative to control samples in both MIA and IS-HIE samples with no significant differences identified between the MIA and IS-HIE groups. MIA samples showed hypermethylation at loci involving craniofacial development and transcription factors important for regulating neurodevelopment and immune function. MIA samples also demonstrated significant hypermethylation at multiple mitochondrial genome CpGs. These findings suggest that maternal inflammation induces epigenetic alterations in fetal brain immune cells that are detectable in neonates. These changes may contribute to heightened neurodevelopmental risk in offspring following hypoxic injury, highlighting potential molecular pathways for future therapeutic targeting.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE319589, at NCBI GEO; found in “Data Availability Statement”

Data Availability Statement

The data presented in this study are openly available in [NCBI GEO accession number GSE319589 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319589)].

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 5 keywords, 15 MeSH terms, 1 funder, 68 references.

Cite

This paper

Ebenezer, A. T., Hicks, J. R., Hollander, B., Hone, A., Batish, M., Akins, R., Marsh, A., & Wright-Jin, E. (2026). Maternal Inflammation Alters Nuclear and Mitochondrial DNA Methylation Patterns in Neonatal Brain Monocytes. Cells, 15(8), 714. https://doi.org/10.3390/cells15080714

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