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

Area of Science:

• Neuroscience
• Immunology
• Epigenetics

Background:

• Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of infant mortality and lifelong neurological disability.
• Maternal infection and inflammation are known risk factors for HIE, but the underlying mechanisms are unclear.
• Epigenetic modifications, such as DNA methylation, are implicated in linking prenatal inflammation to neurodevelopmental outcomes.

Purpose of the Study:

• To investigate the impact of maternal inflammation on DNA methylation patterns in neonatal brain immune cells.
• To compare methylation profiles in offspring exposed to maternal immune activation (MIA) or inflammation-sensitized HIE (IS-HIE) versus controls.
• To identify specific epigenetic alterations associated with maternal inflammation and their potential role in HIE-related neurodevelopmental risks.

Main Methods:

• Utilized a CF-1 mouse model to simulate MIA and IS-HIE conditions.
• Isolated brain monocytes from control and exposed neonates at postnatal day 7.
• Analyzed and compared genome-wide DNA methylation patterns between experimental groups.

Main Results:

• Maternal inflammation significantly altered DNA methylation in neonatal brain monocytes in both MIA and IS-HIE groups compared to controls.
• No significant methylation differences were observed between MIA and IS-HIE groups, suggesting a common inflammatory pathway.
• Hypermethylation was prominent at loci related to craniofacial development, neurodevelopmental transcription factors, immune function, and mitochondrial DNA.

Conclusions:

• Maternal inflammation induces detectable epigenetic alterations in fetal brain immune cells during the neonatal period.
• These inflammation-induced epigenetic changes may contribute to the increased susceptibility to neurodevelopmental disabilities following HIE.
• The identified molecular pathways offer potential targets for future therapeutic interventions aimed at mitigating HIE-related risks.