Placental DNA Methylation Alterations Associated with Maternal Tobacco Smoking at the RUNX3 Gene are also Associated with Gestational Age

Abstract

Aims: The developmental origins of health and disease hypothesis states that later-life disease may be influenced by the quality of the in utero environment. Environmental toxicants can have detrimental effects on fetal development, potentially through effects on placental development and function. Maternal smoking during pregnancy is associated with low birth weight, preterm birth and other complications, and exposure to cigarette smoke in utero has been linked to gross pathologic and molecular changes to the placenta, including differential DNA methylation in placental tissue. The aim of this study was to investigate the relationship between maternal smoking during pregnancy, methylation changes in the placenta and gestational age. Materials & methods: We used Illumina^®‘s (CA, USA) Human Methylation27 BeadChip technology platform to investigate the methylation status of 21,551 autosomal, non-SNP-associated CpG loci in DNA extracted from 206 human placentas and examined loci whose variation in methylation was associated with maternal smoking during pregnancy. Results: We found that methylation patterns of a number of loci within the RUNX3 gene were significantly associated with smoking during pregnancy, and one of these loci was associated with decreased gestational age (p = 0.04). Conclusion: Our findings, demonstrating maternal smoking-induced changes in DNA methylation at specific loci, suggest a mechanism by which in utero tobacco smoke exposure could exert its detrimental effects upon the health of the fetus.

KEYWORDS::

• epigenetics
• gestational age
• in utero
• methylation
• placenta
• pregnancy
• RUNX3
• smoking

Acknowledgements

The authors wish to thank J Lee, G Ferro and K Veiga for their collection of placental samples and recruitment of patients to this study.

Financial & competing interests disclosure

This research was funded by grants R01MH094609 from the NIH National Institute of Mental Health, P20GM103537 from the NIH National Institute of General Medical Sciences, and T32ES007272 from the NIH National Institute of Environmental Health Sciences. 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 conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was funded by grants R01MH094609 from the NIH National Institute of Mental Health, P20GM103537 from the NIH National Institute of General Medical Sciences, and T32ES007272 from the NIH National Institute of Environmental Health Sciences. 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.