Sex-based differences in placental DNA methylation profiles related to gestational age: an NIH ECHO meta-analysis

on behalf of program collaborators for Environmental influences on Child Health Outcomes

Research output: Contribution to journalArticlepeer-review

Abstract

The placenta undergoes many changes throughout gestation to support the evolving needs of the foetus. There is also a growing appreciation that male and female foetuses develop differently in utero, with unique epigenetic changes in placental tissue. Here, we report meta-analysed sex-specific associations between gestational age and placental DNA methylation from four cohorts in the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Programme (355 females/419 males, gestational ages 23–42 weeks). We identified 407 cytosine-guanine dinucleotides (CpGs) in females and 794 in males where placental methylation levels were associated with gestational age. After cell-type adjustment, 55 CpGs in females and 826 in males were significant. These were enriched for biological processes critical to the immune system in females and transmembrane transport in males. Our findings are distinct between the sexes: in females, associations with gestational age are largely explained by differences in placental cellular composition, whereas in males, gestational age is directly associated with numerous alterations in methylation levels.

Original languageEnglish (US)
Article number2179726
JournalEpigenetics
Volume18
Issue number1
DOIs
StatePublished - 2023

Keywords

  • DNA methylation
  • gestational age
  • Placenta
  • sex differences

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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