Poor-quality in utero environments are associated with adverse pregnancy outcomes and susceptibility to early and later life disease. The overarching hypothesis of this work is that methylation profiling in placental tissue will potentially yield biomarkers of in utero exposures and adverse pregnancy and developmental outcomes. The first aim investigated smoking-associated methylation profiles in the placenta using an Illumina Human Methylation27 BeadArray. In 206 placental samples, an association was observed between maternal smoking during pregnancy, placental hypermethylation of one RUNX3 CpG locus, and preterm birth (<37 weeks gestation). The second and third aims investigated placental methylation profiles associated with heavy metal exposure. Specifically, the second aim used an Illumina HumanMethylation450 BeadArray in (n=41) placenta samples and identified 339 CpG loci in the placenta that were significantly associated with infant toenail mercury (Hg), 6 of which were found to be associated in an independent sample set (n=151) with a high-risk NNNS RPMM profile. 110 infant toenail manganese (Mn)-associated CpG loci were also identified in the placenta (n=61) using this array in the third aim, two of which were hypermethylated in the FILIP1L gene, where hypermethylation has been associated in the literature with prostate cancer, a condition also associated with high hair and nail Mn in adults. Together, the three aims of this work better characterize the nature and effects of prenatal exposure to maternal tobacco smoking, Hg, and Mn, provide more complete knowledge of the potential mechanisms that may link prenatal exposures to postnatal outcomes, and contribute to a greater understanding of the developmental origins of health and disease.
Maccani, Jennifer Zeynab Jou,
"Exposure-Related Placental Methylation Changes Are Associated With Adverse Outcomes"
(2013).
Pathobiology Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0XK8CX0
