TY - JOUR
T1 - Dynamic DNA methylation changes in the maternal oxytocin gene locus (OXT) during pregnancy predict postpartum maternal intrusiveness
AU - Toepfer, Philipp
AU - O'Donnell, Kieran J.
AU - Entringer, Sonja
AU - Garg, Elika
AU - Heim, Christine M.
AU - Lin, David T.S.
AU - MacIsaac, Julia L.
AU - Kobor, Michael S.
AU - Meaney, Michael J.
AU - Provençal, Nadine
AU - Binder, Elisabeth B.
AU - Wadhwa, Pathik D.
AU - Buss, Claudia
N1 - Funding Information:
This research was funded by a European Research Area Network (ERA Net) Neuron grant ( MecTranGen 01EW1407A ) and National Institutes of Health grant ( R01 HD-060628 ) awarded to Prof. Claudia Buss as well as NIH grant R01 MH-105538 awarded to Prof. Pathik D. Wadhwa. None of the authors declares any conflict of interest.
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.psyneuen.2019.01.013
DO - 10.1016/j.psyneuen.2019.01.013
M3 - Article
C2 - 30690225
AN - SCOPUS:85060452738
VL - 103
SP - 156
EP - 162
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
SN - 0306-4530
ER -