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

Authors

• Andrew Ebenezer, Thomas Jefferson University
• Jonathan Hicks, Thomas Jefferson University
• Brooke Hollander, Thomas Jefferson UniversityFollow
• Alexander Hone, Thomas Jefferson University
• Mona Batish
• Robert Akins, Thomas Jefferson University
• Adam Marsh
• Elizabeth Wright-Jin, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

4-18-2026

Comments

This article is the author’s final published version in Cells, Volume 15, Issue 8, 2026, Article number 714.

The published version is available at https://doi.org/10.3390/cells15080714. Copyright © 2026 by the authors.

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.

Recommended Citation

Ebenezer, Andrew; Hicks, Jonathan; Hollander, Brooke; Hone, Alexander; Batish, Mona; Akins, Robert; Marsh, Adam; and Wright-Jin, Elizabeth, "Maternal Inflammation Alters Nuclear and Mitochondrial DNA Methylation Patterns in Neonatal Brain Monocytes" (2026). Department of Medicine Faculty Papers. Paper 567.
https://jdc.jefferson.edu/medfp/567

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

42041581

Language

English