DNA methylation profiles in adults born at extremely low birth weight

Karen J Mathewson1, Patrick O McGowan2, Wilfred C de Vega2

  • 1Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada.

Insights

Extremely preterm birth may alter DNA methylation patterns, especially in males, impacting genes related to brain development and metabolism. These epigenetic changes highlight sex-specific long-term effects of extreme prematurity.

Area of Science:

  • Epigenetics
  • Genomics
  • Developmental Biology

Background:

  • Extreme preterm birth can leave lasting biological marks.
  • DNA methylation (DNAm) patterns may record early life stress.
  • Epigenetic changes can influence long-term health outcomes.

Purpose of the Study:

  • To investigate genome-wide DNA methylation differences in adults born extremely preterm versus normal birth weight.
  • To explore potential sex differences in epigenetic responses to extreme preterm birth.
  • To identify biological pathways affected by these epigenetic modifications.

Main Methods:

  • Genome-wide DNA methylation profiling in buccal cells.
  • Comparison of DNAm profiles between extremely low birth weight (ELBW) survivors and normal birth weight (NBW) controls.
  • Gene ontology and network analyses to interpret affected genes.

Main Results:

  • Sex differences in DNAm were significantly amplified in the ELBW group compared to the NBW group.
  • In men, 1,354 DNAm loci across 694 genes differed between ELBW and NBW groups.
  • In women, only two DNAm loci on two genes differed between the groups.
  • Affected genes in ELBW men were enriched in pathways for neuronal development, synaptic transport, and metabolic regulation.

Conclusions:

  • Adults born extremely preterm exhibit distinct DNA methylation profiles, particularly males.
  • Males appear more sensitive to the long-term epigenetic effects of extreme prematurity.
  • These findings suggest synergistic impacts of prenatal adversity and sex on adult epigenomes.

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