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.

神经肽催产素 (OXT) 及其受体 (OXTR) 调节人际关系，尤其是母子互动。在经历过童年虐待 (CM) 的个体中观察到OXTR基因的 DNA 甲基化 (DNAm) 变化。还假设了 OXTR 内的单核苷酸多态性 (SNP) 与 CM 相关的调节作用对 OXTR 的调节。这些CM诱导的表观遗传改变是否由后代生物学遗传仍然未知。因此，我们研究了母体 CM 暴露对 DNAm 和OXTR基因表达可能的代际影响，另外还考虑了三个 SNP 的可能影响：rs53576 和 rs2254298（OXTR基因）和 rs2740210（OXT基因）。我们使用儿童创伤问卷将母亲分为有（CM+）或没有 CM（CM-）的个体。 分娩后从静脉血中分离出母体外周免疫细胞（N  = 117）和从脐带中分离出胎儿免疫细胞（N = 113）。使用 MassARRAY 评估 DNA 甲基化。Taqman 分析用于基因分型和基因表达分析。在母亲中，CM 与OXTR平均甲基化或基因表达无关。然而，与CM+相比，CM-中的四个CpG位点显示出不同的甲基化水平。在母亲中，OXTR rs53576 和OXT rs2740210 等位基因变异与OXTR上的 CM 负载相互作用指甲基化。母体和新生儿的OXTR平均甲基化在 CM- dyads 中呈正相关，但在 CM+ dyads 中没有。我们展示了基因与环境对催产素信号的表观遗传调控的相互作用，并表明OXTR DNAm 的代际可比性可能在 CM+ 母亲的婴儿中发生改变。