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Prenatal lead (Pb) exposure is associated with differential placental DNA methylation and hydroxymethylation in a

Pei Wen Tung1, Elizabeth M Kennedy1, Amber Burt1

  • 1Gangarosa Department of Environmental Health, Emory University, Atlanta, GA, USA.

Epigenetics
|September 23, 2022
PubMed

Insights

Prenatal lead exposure alters placental DNA methylation and hydroxymethylation, impacting pathways crucial for nervous system and organ development. These epigenetic changes highlight potential risks to fetal development from lead exposure.

Area of Science:

  • Environmental Epigenetics
  • Developmental Toxicology
  • Placental Biology

Background:

  • Prenatal lead (Pb) exposure is linked to adverse developmental outcomes.
  • Epigenetic alterations, including DNA methylation and hydroxymethylation, are observed in animal models and newborn blood.
  • The placenta plays a critical role in fetal development, making it a key site for investigating Pb's effects.

Purpose of the Study:

  • To investigate the association between prenatal lead exposure and differential DNA methylation and hydroxymethylation in the placenta.
  • To identify biological pathways affected by lead-associated epigenetic changes in the placenta.
  • To understand how these placental epigenetic modifications may relate to developmental outcomes.

Main Methods:

  • Analysis of maternal and infant toenail and placental samples from a US birth cohort (n=167 maternal, n=172 infant, n=115 placenta).
  • Quantification of DNA methylation and hydroxymethylation using the Illumina Infinium MethylationEPIC BeadChip.
  • Epigenome-wide association study (EWAS) and overrepresentation analysis (ConsensusPathDB) to identify Pb-associated epigenetic sites and affected pathways.

Main Results:

  • Prenatal lead exposure was associated with significant differential methylation at 480 sites (maternal toenail), 27 sites (infant toenail), and 2 sites (placenta).
  • Differential hydroxymethylation was identified at 2 sites (maternal toenail), 1 site (infant toenail), and 14 sites (placenta), with most showing increased hydroxymethylation.
  • Affected pathways included those involved in nervous system development, organ development, calcium transport, and signaling activities.

Conclusions:

  • Prenatal lead exposure induces variable DNA methylation and hydroxymethylation in the placenta.
  • These epigenetic alterations in the placenta affect critical biological pathways potentially impacting placental function and fetal development.
  • The findings underscore the role of placental epigenetics in mediating the adverse effects of prenatal lead exposure.

Keywords:
DNA methylationEWASepigeneticshydroxymethylationleadplacenta

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