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

PSYCHONEUROENDOCRINOLOGY

卷:103

Article

Toepfer, Philipp^1,2,3,4  O'Donnell, Kieran J.^5,6  Entringer, Sonja^1,2,3,4,13  Garg, Elika⁵  Heim, Christine M.^1,2,3,4,7  Lin, David T. S.⁸  MacIsaac, Julia L.⁸  Kobor, Michael S.⁸  Meaney, Michael J.^5,6,9  Provencal, Nadine^10,11  Binder, Elisabeth B.^10,12  Wadhwa, Pathik D.^13,14,15,16  Buss, Claudia^1,2,3,4,13 

[1] Charite Univ Med Berlin, Luisenstr 57, D-10117 Berlin, Germany

[2] Free Univ Berlin, Luisenstr 57, D-10117 Berlin, Germany

[3] Humboldt Univ, Luisenstr 57, D-10117 Berlin, Germany

[4] BIH, Inst Med Psychol, Luisenstr 57, D-10117 Berlin, Germany

[5] McGill Univ, Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinfomat & Mental Hlth, Montreal, PQ, Canada

[6] McGill Univ, Sackler Program Epigenet & Psychobiol, Montreal, PQ, Canada

[7] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA

[8] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC, Canada

[9] Singapore Inst Clin Sci, Singapore, Singapore

[10] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany

[11] Simon Fraser Univ, Fac Hlth Sci, Vancouver, BC, Canada

[12] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA

[13] Univ Calif Irvine, Dev Hlth & Dis Res Program, Orange, CA 92668 USA

[14] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Irvine, CA 92717 USA

[15] Univ Calif Irvine, Sch Med, Dept Obstet & Gynecol, Irvine, CA 92717 USA

[16] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA

关键词: Oxytocin;    Maternal behavior;    DNA methylation;    Behavioral epigenetics;    Estrogen sensitivity;    Pregnancy;   

DOI  :  10.1016/j.psyneuen.2019.01.013

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free