Sharma, R. ; Frasch, M.G.* ; Zelgert, C.* ; Zimmermann, P.* ; Fabre, B.* ; Wilson, R. ; Waldenberger, M. ; MacDonald, J.W.* ; Bammler, T.K.* ; Lobmaier, S.M.* ; Antonelli, M.C.*
Maternal-fetal stress and DNA methylation signatures in neonatal saliva: An epigenome-wide association study.
Clin. Epigenet. 14:87 (2022)
BACKGROUND: Maternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant's neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA. RESULTS: A total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a 'Fetal Stress Index' (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn's saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D. CONCLUSIONS: Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.
Impact Factor
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Times Cited
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Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Pregnancy ; Prenatal Stress ; Perceived Stress ; Biomarkers ; Newborn Saliva ; Dna Methylation ; Cortisol ; Epigenetics ; Ewas
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2022
Prepublished im Jahr
HGF-Berichtsjahr
2022
ISSN (print) / ISBN
1868-7075
e-ISSN
1868-7083
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 14,
Heft: 1,
Seiten: ,
Artikelnummer: 87
Supplement: ,
Reihe
Verlag
Springer
Verlagsort
Berlin : Heidelberg
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504091-001
Förderungen
Institute for Advanced Study, Technische Universität München
Technische Universität München
Health Foundation of South Florida
Intellectual and Developmental Disabilities Research Center
University of Washington
Klinikum rechts der Isar, Technical University of Munich
Klinikum rechts der Isar
Klinik und Poliklinik für Frauenheilkunde
IAS-TUM
Department of Obstetrics and Gynecology
Copyright
Erfassungsdatum
2022-07-27