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Fernández Boyano, Icíar

University of British Columbia

A growing body of research has identified molecular and histological alterations in the placenta linked to preeclampsia (PE). Studies of placental DNA methylation (DNAme) and gene expression have uncovered molecular subtypes of PE, which correspond to specific placental histological features and clinical presentations of the disease. However, the considerable clinical and molecular variability within and across PE subtypes makes the condition challenging to study. PE is most strongly associated with placental abnormalities and poor outcomes for both mother and fetus when it occurs early in pregnancy. In addition, PE exhibits sex-associated incidence patterns, with male fetuses at a higher risk for late-onset PE (LOPE) and females at higher risk of early-onset PE (EOPE). Nevertheless, whether there is an interaction between sex and PE that affects DNAme in the placenta has not yet been explored. Similarly, EOPE-associated changes have only been reported on the autosomes, but not investigated on the X chromosome. In this dissertation, I developed a model that relies on a 45-CpG DNAme signature to predict a homogeneous placental phenotype of EOPE in a categorical or continuous manner (assigning a probability). I also found several EOPE-associated DNAme changes on the X chromosome, whereas I did not observe any interaction between sex and EOPE on autosomal DNAme. Lastly, I created an integrated knowledge translation initiative, titled “Know Your Placenta,” to disseminate scientific information about the human placenta and its research tailored to a lay audience, specifically pregnant individuals and parents.

Text

2025-01-22

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/90187

Genome Science and Technology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/