No long-term effects of antenatal synthetic glucocorticoid exposure on epigenetic regulation of stress-related genes.
Adolescent
Child
Cross-Sectional Studies
DNA Methylation
Epigenesis, Genetic
Female
Glucocorticoids
/ metabolism
Humans
Hydrocortisone
Hypothalamo-Hypophyseal System
/ metabolism
Pituitary-Adrenal System
/ metabolism
Pregnancy
Receptors, Glucocorticoid
/ genetics
Serotonin Plasma Membrane Transport Proteins
/ genetics
Stress, Psychological
/ metabolism
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
16 02 2022
16 02 2022
Historique:
received:
16
09
2021
accepted:
04
01
2022
revised:
10
12
2021
entrez:
17
2
2022
pubmed:
18
2
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis "functioning". The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning.
Identifiants
pubmed: 35173143
doi: 10.1038/s41398-022-01828-x
pii: 10.1038/s41398-022-01828-x
pmc: PMC8850596
doi:
Substances chimiques
Glucocorticoids
0
Receptors, Glucocorticoid
0
SLC6A4 protein, human
0
Serotonin Plasma Membrane Transport Proteins
0
Hydrocortisone
WI4X0X7BPJ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
62Informations de copyright
© 2022. The Author(s).
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