A Cross-Generational Methylomic Signature of Infant Maltreatment in Newborn Rhesus Macaques

Area of Science:

• Epigenetics
• Developmental Psychology
• Comparative Medicine

Background:

• Early-life adversity (ELA) causes lasting physical and mental health issues.
• ELA's effects can span generations, potentially through epigenetic modifications.
• Nonhuman primates offer a translational model for studying ELA's cross-generational impact.

Purpose of the Study:

• To investigate the cross-generational epigenetic and functional consequences of physical maltreatment and neglect.
• To bridge the gap between rodent models and human clinical studies of ELA.

Main Methods:

• Methylomic profiling using the Illumina MethylationEPIC array in rhesus macaques.
• Comparison of 339,081 methylation sites between offspring of maltreated and non-maltreated mothers.
• Analysis of neonatal blood cortisol levels.

Main Results:

• Identified 409 differentially methylated positions (DMPs) and 7 differentially methylated regions linked to cross-generational maltreatment.
• Offspring of maltreated mothers had significantly lower neonatal blood cortisol levels.
• 137 DMPs associated with human traits, including child abuse and glucocorticoid exposure, with 19 potentially mediating the cortisol association.

Conclusions:

• Epigenetic alterations play a role across generations following environmental insults.
• These epigenetic changes may influence the development of phenotypic alterations in offspring exposed to maltreatment.
• Findings deepen understanding of intergenerational transmission of health risks associated with ELA.