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Distress During Pregnancy: Epigenetic Regulation of Placenta Glucocorticoid-Related Genes and Fetal Neurobehavior
Open accessAbstract
OBJECTIVE: 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. METHOD: 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. RESULTS: 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 (β=-0.51), and modestly elevated methylation of FKBP5, also with lower fetal coupling (β=-0.47). These increases in methylation were validated by bisulfite sequencing, where they occurred in a minority of clones. CONCLUSIONS: 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.
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“Placental hypermethylation across NR3C1 and FKBP5 has been associated with higher second trimester perceived stress and increased anxious and depressive symptoms, in case of FKBP5 in 61 women (Monk et al., 2016)”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Monk et al., 2016
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“perceived stress was associated with increased FKBP5 methylation which in turn was associated with lower third trimester fetal coupling (correlation of fetal movement and heart rate; indicative of CNS maturation), denoting an epigenetic link between pregnancy stress and fetal development (Monk et al., 2016)”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Monk et al., 2016
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“↑ FKBP5 methylation associated with increased perceived stress”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Monk et al., 2016
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Metadata
- Authors
- Monk, C., Feng, T., Lee, S., Krupska, I., Champagne, F. A., & Tycko, B.
- Affiliations
- Columbia University Irving Medical Center (US)
- Venue
- American Journal of Psychiatry
- Published
- 2016-07-01
- Volume
- 173
- Issue
- 7
- Pages
- 705-713
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5026410
- OpenAlex
- W2304339492
- Cited by
- 304
- References
- 40
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 32 · 2023: 19 · 2022: 28 · 2021: 39 · 2020: 61 · 2019: 21 · 2018: 32 · 2017: 23 · 2016: 10
- FWCI
- 28.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH092580)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- maternal distress, prenatal stress, placenta, DNA methylation, glucocorticoid pathway, 11β-hydroxysteroid dehydrogenase type 2, NR3C1, FKBP5, fetal heart rate, fetal movement, fetal neurobehavior, salivary cortisol, epigenetic regulation
- MeSH terms
- Tacrolimus Binding Protein 5, Adolescent, Adult, Anxiety Disorders, Arousal, Depressive Disorder, Female, Fetal Movement, Heart Rate, Fetal, Humans, Hydrocortisone, Infant, Newborn, Placenta, Pregnancy, Pregnancy Trimester, Third, Prenatal Exposure Delayed Effects, Receptors, Glucocorticoid, CpG Islands, DNA Methylation, Mood Disorders, Tacrolimus Binding Proteins, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Epigenesis, Genetic, Young Adult
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