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Abstract

Exposure to prenatal maternal stress during pregnancy has been associated with several adverse perinatal outcomes, such as pre-term birth, fetal growth restriction, and altered cognitive development. As the interface between the fetal and maternal compartments during pregnancy, the placenta has been heavily implicated in this process. The placenta is responsible for inactivating maternal cortisol, which increases during periods of stress, to limit fetal exposure. Few studies have identified associations between prenatal maternal stress exposures and epigenetic changes, such as changes in DNA methylation. DNA methylation is a highly researched epigenetic mark associated with gene expression patterns. Despite this, studies investigating the effects of prenatal maternal stress on the placental methylome remain relatively limited. In this thesis, I used DNA methylation data collected from the Illumina Infinium MethylationEPIC BeadChip microarray from placentas in two cohorts: QF2011, a cohort exposed to an environmental disaster, and SPAH, a cohort exposed to differing levels of socioeconomic disparities. I investigated if there were placental DNA methylation changes associated with prenatal maternal stress exposures on both the autosomes and sex chromosomes, and if these changes were altered depending on the timing of exposure during gestation and/or fetal sex. This included determining if there were differences in methylation at specific sites across the genome via epigenome-wide association studies, as well as using epiphenotyping approaches to investigate cellular composition and epigenetic age acceleration changes. I found that there were no large impacts of prenatal maternal stress on the placental DNA methylome. However, in both cohorts, there were associations between higher prenatal maternal stress and accelerated placental epigenetic age. I also saw that, while not associated with maternal stress, there were significant differences in the trophoblast cell ratio between XX and XY samples, with XX placentas having higher cytotrophoblast:syncytiotrophoblast than XY placentae. Through these studies, I contributed to the current literature aiming to understand the biology underlying adverse fetal outcomes seen with in utero exposure to maternal stressors. I did this by identifying that while global DNA methylation is not greatly influenced by the maternal stressors examined, placental epigenetic age acceleration may be a potential mechanism for follow-up studies.