Dynamic DNA methylation changes in the maternal oxytocin gene locus ( OXT ) during pregnancy predict postpartum maternal intrusiveness

作者：Philipp Toepfer; Kieran J O’Donnell; Sonja Entringer; Elika Garg; Christine M Heim; David T S Lin; Julia L MacIsaac; Michael S Kobor; Michael J Meaney; Nadine Provenal; Elisabeth B Binder; Pathik D Wadhwa; Claudia Buss

来源：Psychoneuroendocrinology, 2019, 156-162.

DOI：10.1016/j.psyneuen.2019.01.013

• Oxytocin
• Maternal behavior
• DNA methylation
• Behavioral epigenetics
• Estrogen sensitivity
• Pregnancy

Abstract(#br)Maternal behavior (MB) is observable across mammals and represents an important feature of environmental variation during early postnatal development. Oxytocin (OT) plays a crucial role in MB. Even prior to childbirth, pregnancy induces epigenetic and other downstream changes in the maternal OT-system, likely mediated by the actions of steroid hormones. However, little is known about the nature and consequences of epigenetic modifications in the maternal OT-encoding gene ( OXT ) during pregnancy. Our study aims to investigate temporal dynamics of OXT promoter DNA methylation (DNAm) throughout pregnancy in predicting MB in humans. In 107 mother-child dyads, maternal OXT DNAm was serially analyzed in whole blood in early, mid and late pregnancy. MB was coded based on standardized mother-child interactions at six months postpartum. After controlling for cellular heterogeneity, race/ethnicity, age, and socioeconomic status, OXT -promoter DNAm exhibited a dynamic profile during pregnancy ( b = 0.026, t =-3.37, p < .001), with decreases in DNAm from early to mid-pregnancy and no further change until late pregnancy. Moreover, dynamic DNAm trajectories of the OXT -promoter region predicted MB (intrusiveness) at six months postpartum ( b = 0.006, t = 2.0, p < 0.05), with 6% higher OXT DNAm in late pregnancy in intrusive compared to non-intrusive mothers. We here demonstrate that OXT promoter DNAm changes significantly throughout gestation in peripheral blood and that these changes are associated with variability in MB, providing a novel potential biomarker predicting postnatal MB.

• 单位
  emory university school of medicine