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The neuropeptide oxytocin (OXT) and its receptor (OXTR) modulate interpersonal relationships, particularly mother–child interactions. DNA methylation (DNAm) changes of the  OXTR  gene were observed in individuals who experienced Childhood Maltreatment (CM). A modulatory role of single nucleotide polymorphisms (SNP) within  OXTR  in association with CM on the regulation of OXTR was also postulated. Whether these CM-induced epigenetic alterations are biologically inherited by the offspring remains unknown. We thus investigated possible intergenerational effects of maternal CM exposure on DNAm and  OXTR  gene expression, additionally accounting for the possible influence of three SNP: rs53576 and rs2254298 ( OXTR  gene), and rs2740210 ( OXT  gene). We used the  Childhood Trauma Questionnaire  to classify mothers into individuals with (CM+) or without CM (CM−). Maternal peripheral immune cells were isolated from venous blood ( N  = 117) and fetal immune cells from the umbilical cord ( N  = 113) after parturition. DNA methylation was assessed using MassARRAY. Taqman assays were performed for genotyping and gene expression analyses. Among mothers, CM was not associated with  OXTR  mean methylation or gene expression. However, four CpG sites showed different methylation levels in CM− compared to CM+. In mothers, the  OXTR  rs53576 and  OXT  rs2740210 allelic variations interacted with CM load on the  OXTR  mean methylation. Maternal and newborns’ mean methylation of  OXTR  were positively associated within CM− dyads, but not in CM+ dyads. We show gene×environment interactions on the epigenetic regulation of the oxytocinergic signaling and show the intergenerational comparability of the  OXTR  DNAm might be altered in infants of CM+ mothers.

Associations between childhood maltreatment and DNA methylation of the oxytocin receptor gene in immune cells of mother–newborn dyads