Placental Epigenetic Patterning of Glucocorticoid Response Genes is Associated with Infant Neurodevelopment

Abstract

Aim: To determine associations between methylation of NR3C1, HSD11B2, FKBP5 and ADCYAP1R1 and newborn neurobehavioral outcomes. Methods: In 537 newborns, placental methylation was quantified using bisulfite pyrosequencing. Profiles of neurobehavior were derived via the Neonatal Intensive Care Unit Network Neurobehavioral Scales. Using exploratory factor analysis, the relationships between methylation factor scores and neurobehavioral profiles were examined. Results: Increased scores of the factor characterized by NR3C1 methylation were associated with membership in a reactive, poorly regulated profile (odds ratio: 1.47; 95% CI: 1.00–2.18), while increased scores of the factor characterized by HSD11B2 methylation reduced this risk. Conclusion: These results suggest that coordinated regulation of these genes influences neurobehavior and demonstrates the importance of examining these alterations in a harmonized fashion.

Keywords::

• ADCYAP1R1
• fetal basis of adult disease
• FKBP5
• glucocorticoids
• HSD11B2
• neurobehavior
• NR3C1
• placenta

Acknowledgements

The authors would like to thank the staff at Women and Infants Hospital, particularly J Lee and E Oliveira for their help with the data collection, as well as A Roberts, R John and L Kwan for their assistance with biological processing and data entry. We would also like to acknowledge M Karagas, B Christensen and L Stroud for their guidance with this paper.

Disclaimer

The articles contents are solely the responsibility of the grantee and do not necessarily represent the official views of the US EPA. Further, the US EPA does not endorse the purchase of any commercial products or services mentioned in the publication. The sponsors of this research had no role in study design, analysis and interpretation of data, in writing of the report or decision to submit the report for publication.

Financial & competing interests disclosure

This work is supported by NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223 and NIH-NIEHS P01 ES022832/EPA RD83544201. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work is supported by NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223 and NIH-NIEHS P01 ES022832/EPA RD83544201. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.