DNA Methylation of Imprinted Genes in Mexican–American Newborn Children with Prenatal Phthalate Exposure

Abstract

Aim: Imprinted genes exhibit expression in a parent-of-origin-dependent manner and are critical for child development. Recent limited evidence suggests that prenatal exposure to phthalates, ubiquitous endocrine disruptors, can affect their epigenetic dysregulation. Materials & methods: We quantified DNA methylation of nine imprinted gene differentially methylated regions by pyrosequencing in 296 cord blood DNA samples in a Mexican–American cohort. Fetal exposure was estimated by phthalate metabolite concentrations in maternal urine samples during pregnancy. Results: Several differentially methylated regions of imprinted genes were associated with high molecular weight phthalates. The most consistent, positive, and false discovery rate significant associations were observed for MEG3. Conclusion: Phthalate exposure in utero may affect methylation status of imprinted genes in newborn children.

Keywords::

• cord blood
• differentially methylated region
• DNA methylation
• endocrine disruptors
• imprinted genes
• in utero exposure
• Mexican–Americans
• newborns
• phthalates
• pyrosequencing

Author’s contributions

G Tindula, N Holland, C Hoyo, B Eskenazi and SK Murphy conceived and designed the study; A Bradman, K Huen and Z Huang provided expert guidance in study design and manuscript review; G Tindula, C Grenier and ME Fung analyzed the data; and G Tindula and N Holland wrote the manuscript. All authors read, edited and approved the manuscript prior to submission.

Acknowledgements

The authors would like to thank all CHAMACOS participants and field staff for contributing to this study. We are also grateful to A Calafat and X Ye for their help with measuring phthalate metabolite concentrations.

Disclaimer

The interpretations of the study findings pertain to the authors alone, and do not reflect the official views of NIEHS, the US EPA, Duke University, NC State University or the University of California, Berkeley.

Financial & competing interests disclosure

This publication was made possible by grants from the National Institute of Environmental Health Sciences (NIEHS) [P01 ES009605, R01 ES021369, R01 ES023067, R24 ES028529, F31 ES027751], the NIH [UG3OD023356], and from the US Environmental Protection Agency (EPA) [R82670901, and RD83451301] (G Tindula, K Huen, ME Fung, A Bradman, B Eskenazi, N Holland). Contributions by SK Murphy, C Hoyo, Z Huang and C Grenier were supported by the National Institute of Environmental Health Sciences [P01 ES022831] and by the US Environmental Protection Agency [RD83543701]. 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.

Ethical disclosure

The authors state that they have obtained appropriate institutional review board approval for all human experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This publication was made possible by grants from the National Institute of Environmental Health Sciences (NIEHS) [P01 ES009605, R01 ES021369, R01 ES023067, R24 ES028529, F31 ES027751], the NIH [UG3OD023356], and from the US Environmental Protection Agency (EPA) [R82670901, and RD83451301] (G Tindula, K Huen, ME Fung, A Bradman, B Eskenazi, N Holland). Contributions by SK Murphy, C Hoyo, Z Huang and C Grenier were supported by the National Institute of Environmental Health Sciences [P01 ES022831] and by the US Environmental Protection Agency [RD83543701]. 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.