A cross-generational methylomic signature of infant maltreatment in newborn rhesus macaques.

Abstract

Background: Early life adversity (ELA) result in detrimental physical and mental health outcomes. The impact of ELA can reverberate across generations, with epigenetic modifications being one of the proposed biological correlates of exposure to ELA. Here we bridge the translational gap between rodent models and clinical studies by utilizing a nonhuman primate model to study the cross-generational epigenetic and functional footprints of physical maltreatment and neglect.

Methods: Methylomic profiling was performed using the Illumina MethylationEPIC array platform, adapted for rhesus macaques. 339,081 individual methylation sites were compared between newborn offspring of maltreated (n = 14, 8 female) and non-maltreated (n = 12, 5 female) mothers.

Results: We identified 409 differentially methylated positions (DMPs) and 7 differentially methylated regions associated with the cross-generational impact of infant maltreatment. A subsequent pathway enrichment analysis revealed 78 enriched pathways. Neonatal blood cortisol levels were significantly lower in animals with a maltreated mother (maltreated n = 13, 7 female; control n = 9, 4 female). Out of the 409 DMPs, 46 showed an association with blood cortisol levels, of which 19 were found to potentially mediate the association between ancestral infant maltreatment and decreased blood cortisol levels. Finally, 137 of the DMPs were associated with a human trait in the EWAS Atlas, including child abuse and glucocorticoid exposure.

Conclusions: These findings provide a deeper insight into the role of epigenetic alterations across generations after environmental insults and how this may impact the development of phenotypic alterations in offspring of maltreatment exposed individuals.