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Distress During Pregnancy: Epigenetic Regulation of Placenta Glucocorticoid-Related Genes and Fetal Neurobehavior.

ABSTRACT: Increased risk of psychopathology is observed in children exposed to maternal prenatal distress, and elevated maternal cortisol and epigenetic regulation of placental glucocorticoid-pathway genes are potential mechanisms. The authors examined maternal distress and salivary cortisol in relation to fetal movement and heart rate ("coupling") and DNA methylation of three glucocorticoid pathway genes-HSD11B2, NR3C1, and FKBP5-in term placentas.Mood questionnaires and salivary cortisol were collected from 61 women between 24-27 gestational weeks, and fetal assessment was conducted at 34-37 weeks. Placental CpG methylation in the three genes was analyzed using 450K Beadchips and bisulfite sequencing; correlations between maternal and fetal variables and DNA methylation were tested; and maternal distress effects on fetal behavior via DNA methylation were investigated.Perceived stress (Perceived Stress Scale), but not cortisol, was associated with altered CpG methylation in placentas. In the highest tertile of the Perceived Stress Scale, the Beadchip data revealed modestly elevated methylation of HSD11B2, associated with lower fetal coupling (?=-0.51), and modestly elevated methylation of FKBP5, also with lower fetal coupling (?=-0.47). These increases in methylation were validated by bisulfite sequencing, where they occurred in a minority of clones.This is the first study to link the effects of pregnant women's distress on the fetus and epigenetic changes in placental genes. Since increased DNA methylation in HSD11B2 and FKBP5 are seen in a minority of bisulfite sequencing clones, these epigenetic changes, and functional consequences, may affect subpopulations of placental cells.

SUBMITTER: Monk C

PROVIDER: S-EPMC5026410 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Distress During Pregnancy: Epigenetic Regulation of Placenta Glucocorticoid-Related Genes and Fetal Neurobehavior.

Monk Catherine C Feng Tianshu T Lee Seonjoo S Krupska Izabela I Champagne Frances A FA Tycko Benjamin B

The American journal of psychiatry 20160325 7

<h4>Objective</h4>Increased risk of psychopathology is observed in children exposed to maternal prenatal distress, and elevated maternal cortisol and epigenetic regulation of placental glucocorticoid-pathway genes are potential mechanisms. The authors examined maternal distress and salivary cortisol in relation to fetal movement and heart rate ("coupling") and DNA methylation of three glucocorticoid pathway genes-HSD11B2, NR3C1, and FKBP5-in term placentas.<h4>Method</h4>Mood questionnaires and ...[more]

PMID: 27013342

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Project description:BackgroudWe have recently reported that maternal prenatal pregnancy-related anxiety predicts preschoolers' emotional and behavioral development in a gender-dependent manner. This study aims to test for this gender-specific effect in a different cohort and investigate whether the gender difference was specific to placental methylation of genes regulating glucocorticoids.MethodsA total of 2405 mother-child pairs from the Ma'anshan Birth Cohort Study were included in present study. The maternal pregnancy-related anxiety symptoms were evaluated with the Pregnancy-Related Anxiety Questionnaire in the third trimester of pregnancy. Child neurobehavior was assessed with the Strengths and Difficulties Questionnaire at 4 years old. Placental methylation of FKBP5, NR3C1 and HSD11B2 genes was quantified using the MethylTarget approach in 439 pregnant women. After exploratory factor analysis, the associations between methylation factor scores and pregnancy-related anxiety and child neurobehavior were examined using logistic regression analysis.ResultsAfter controlling for confounding factors, pregnancy-related anxiety in the third trimester of pregnancy increased the risk of hyperactivity only in boys and emotional symptoms only in girls. Decreased scores of the factor characterized by FKBP5 methylation were associated with maternal pregnancy-related anxiety only in boys. Furthermore, increased scores of the factors characterized by NR3C1 and HSD11B2 methylation were associated with hyperactivity (NR3C1: adjusted OR = 1.80, 95%CI = 1.15-2.83) and emotional symptoms (HSD11B2: adjusted OR = 0.53, 95%CI = 0.29-0.97; NR3C1: adjusted OR = 1.64, 95%CI = 1.03-2.59) only in boys. However, the scores of the factor characterized by FKBP5, NR3C1 and HSD11B2 did not mediate the relationship between maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity.ConclusionsOur results suggested that pregnancy-related anxiety in the third trimester of pregnancy predicted preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner. Although we did not find the mediation role of the placental methylation of genes regulating glucocorticoids, we found it was associated with both maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner.

Dataset Information

Distress During Pregnancy: Epigenetic Regulation of Placenta Glucocorticoid-Related Genes and Fetal Neurobehavior.

Publications

Distress During Pregnancy: Epigenetic Regulation of Placenta Glucocorticoid-Related Genes and Fetal Neurobehavior.

Similar Datasets

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