ArticleProceedings of the National Academy of Sciences of the United States of America2020
Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 5 of them syntheses that pooled it.
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Who cites it
114 citing papers in PubMed, 5 syntheses or guidelines pooled it, 214 citations in OpenAlex.
- Epigenetic effects of endogenous and exogenous glucocorticosteroids during pregnancy on the offspring: a systematic-narrative review.Hormones (Athens, Greece) · 2025Pooled it
- From placenta to the foetus: a systematic review of in vitro models of stress- and inflammation-induced depression in pregnancy.Molecular psychiatry · 2025Pooled it
- Acute and long-term effects of adolescence stress exposure on rodent adult hippocampal neurogenesis, cognition, and behaviour.Molecular psychiatry · 2023Pooled it
- A systematic review of neuroimaging epigenetic research: calling for an increased focus on development.Molecular psychiatry · 2023Pooled it
- The effect of adverse childhood experiences on chronic pain and major depression in adulthood: a systematic review and meta-analysis.British journal of anaesthesia · 2023Pooled it
- Multi-omics characterization of chronic social defeat stress recall-activated nuclei in Arc-GFP mice.Molecular psychiatry · 2026Article
- A Critical Review of Longitudinal DNA Methylomic Changes Associated with Treatment Response in Major Depressive Disorder.International journal of molecular sciences · 2026Review
- Glucocorticoid Signaling in PSC-Derived Neural Systems to Elucidate Mechanisms of Stress-Induced Psychiatric Vulnerability.Molecular neurobiology · 2026Review
- Sexually-dimorphic offspring outcomes following antenatal corticosteroids: a review of the evidence for congenital adrenal hyperplasia and preterm birth risk.Biology of sex differences · 2026Review
- Glucocorticoids and cell fate in the developing brain: Neuroendocrine mechanisms shaping developmental trajectories.Journal of neuroendocrinology · 2026Review
- Epigenetic Modulation by Vitamin C and in Prenatal Depression: Implications for Offspring Health.Current medical science · 2026Review
- Stress-induced epigenome changes as a risk factor in the onset of mental disorders.Frontiers in psychiatry · 2026Review
- A polyepigenetic glucocorticoid exposure score and HPA axis-related DNA methylation are associated with gestational epigenetic aging.Epigenetics · 2025Article
- Toward Understanding and Halting Legacies of Trauma.Biological psychiatry · 2025Review
- Exploring the relationship between methylation of the cortisol receptor genes and brain and cognitive outcomes in individuals with elevated amyloid-β.Research square · 2025Article
- Comprehensive Review of the Impact of Maternal Stress on Fetal Development.Pediatric discovery · 2025Review
- Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees.Scientific reports · 2025Article
- Glucocorticoid exposure-induced alterations in epigenetic age from human preterm infants and human lung fibroblasts and hippocampal neuronal cells.Clinical epigenetics · 2025Article
- Stress Molecular Signaling in Interaction With Cognition.Biological psychiatry · 2025Review
- Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids.Science advances · 2025Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 9 institutions in 6 countries.
Funding
Abstract
Prenatal stress exposure is associated with risk for psychiatric disorders later in life. This may be mediated in part via enhanced exposure to glucocorticoids (GCs), which are known to impact neurogenesis. We aimed to identify molecular mediators of these effects, focusing on long-lasting epigenetic changes. In a human hippocampal progenitor cell (HPC) line, we assessed the short- and long-term effects of GC exposure during neurogenesis on messenger RNA (mRNA) expression and DNA methylation (DNAm) profiles. GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts (false discovery rate [FDR] ≤ 0.1 and absolute fold change [FC] expression ≥ 1.15). HPC expression and GC-affected DNAm profiles were enriched for changes observed during human fetal brain development. Differentially methylated sites (DMSs) with GC exposure clustered into 4 trajectories over HPC differentiation, with transient as well as long-lasting DNAm changes. Lasting DMSs mapped to distinct functional pathways and were selectively enriched for poised and bivalent enhancer marks. Lasting DMSs had little correlation with lasting expression changes but were associated with a significantly enhanced transcriptional response to a second acute GC challenge. A significant subset of lasting DMSs was also responsive to an acute GC challenge in peripheral blood. These tissue-overlapping DMSs were used to compute a polyepigenetic score that predicted exposure to conditions associated with altered prenatal GCs in newborn's cord blood DNA. Overall, our data suggest that early exposure to GCs can change the set point of future transcriptional responses to stress by inducing lasting DNAm changes. Such altered set points may relate to differential vulnerability to stress exposure later in life.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.