EDCs potential long-lasting effects on children’s neurodevelopment

Placental CpG methylation of HPA-axis genes is associated with cognitive impairment at age 10 among children born extremely preterm

2018 Study Highlights

  • Placental CpG methylation in relation to cognition at age 10 was evaluated.
  • Ten HPA axis-associated genes were associated with cognitive function.
  • The transcriptional regulator MECP2 was enriched within the ten HPA axis genes.
  • Placental CpG methylation in the context of fetal development is discussed.
  • This study relates to the developmental origins of health and disease hypothesis.


The results of this study highlight a set of 10 HPA axis-associated genes that displayed an association between increased placental CpG methylation and either moderate/severe cognitive impairment or low/low normal cognitive function at age 10 years. Many of these genes regulate both placental function and HPA axis function. The identified genes are also known to play integral roles in memory, learning, and the development of psychological disorders and there is evidence that exposure to EDCs may influence their expression as well. Furthermore, given the plasticity of the epigenome during the prenatal period, these alterations could be influenced by exposure to environmental contaminants, including EDCs. Growing research supports that exposure to common EDCs, including estrogenic compound like BPA, may dysregulate several genes involved in regulation of the HPA axis. This work provides a basis for which to subsequently investigate the role of EDCs on the HPA axis. Future work should incorporate exposure data as it relates to epigenetic modifications of the HPA axis-associated genes, as these data could provide more information as to how EDCs mechanistically disrupt the HPA axis and potentially provide biomarkers for exposure and laterlife cognitive impairments in mid-childhood.