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Updated: Jul 14, 2025
A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure
Published on: October 24, 2018
Neonatal stress exposure and DNA methylation of stress-related and neurodevelopmentally relevant genes: An
Nienke H van Dokkum1, Mian Bao2, Rikst Nynke Verkaik-Schakel2
1Division of Neonatology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Insights
Neonatal Intensive Care Unit (NICU) stress may alter DNA methylation in preterm infants. This study explored associations between stress exposure and gene methylation, suggesting potential long-term neurodevelopmental impacts.
Area of Science:
- Neonatal care
- Epigenetics
- Neurodevelopment
Background:
- Neonatal Intensive Care Unit (NICU) stress can impact neurodevelopment in preterm infants.
- Altered DNA methylation in stress-related genes may be a key mechanism.
Purpose of the Study:
- To investigate the association between neonatal stress exposure and DNA methylation in specific genes.
- To examine DNA methylation at two time points during NICU stay: early and at discharge.
Main Methods:
- Prospective cohort study of 45 extremely preterm infants (24-30 weeks gestation).
- Collected fecal samples for DNA methylation analysis of 10 stress-related genes using pyrosequencing.
- Quantified daily stress using the Neonatal Infant Stressor Scale (NISS) and analyzed associations with DNA methylation.
Main Results:
- Most gene methylation levels remained stable between early NICU stay and discharge, with OPRM1 showing a difference.
- Correlations between cumulative NISS scores and DNA methylation at discharge were observed for several genes (NR3C1, SLC6A4, SLC1A2, IGF2, BDNF, OPRM1), though not statistically significant.
Conclusions:
- Neonatal stress exposure may influence the regulation of stress-related and neurodevelopmental genes.
- Larger studies are needed to confirm these findings and investigate effects on gene expression.
Background:
Stress exposure during Neonatal Intensive Care Unit (NICU) stay may have long-lasting effects on neurodevelopmental outcomes in extremely preterm infants. Altered DNA methylation of stress-related and neurodevelopmentally relevant genes may be an underlying mechanism.
Aims:
This exploratory study aimed to investigate the association between neonatal stress exposure and DNA methylation in these genes at two different time points: early during the NICU stay (7-14 days after birth) and later, at discharge from the NICU.
Subjects:
We included 45 extremely preterm infants in this prospective cohort study, gestational age 24-30 weeks.
Outcome Measures:
We collected fecal samples at days 7-14 (n = 44) and discharge (n = 28) and determined DNA methylation status in predefined regions of NR3C1, SLC6A4, HSD11B2, OPRM1, SLC7A5, SLC1A2, IGF2, NNAT, BDNF and GABRA6 using pyrosequencing. Because of low DNA concentrations in some fecal samples, we could do so in 25-50 % of collected samples. We prospectively quantified daily neonatal stress exposure using the Neonatal Infant Stressor Scale (NISS) and explored associations between cumulative NISS scores and average DNA methylation status.
Results:
Rates of methylation of most genes were not statistically different between day 7-14 and discharge, except for OPRM1. We found moderately high and mostly negative correlation coefficients upon discharge with the cumulative NISS for the NR3C1, SLC6A4, SLC1A2, IGF2, BDNF and OPRM1 genes, albeit not statistically significant.
Conclusions:
Findings suggest that expression of stress-related and neurodevelopmentally relevant genes may be differently regulated following higher neonatal stress exposure. Larger studies should challenge the findings of this study and ideally test the effects on gene expression.
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