PhD defence M.M. (Marjolein) van Vliet

Below is a brief summary of the dissertation:

Part I of this thesis investigates one‐carbon moieties and parental characteristics in relation to placental DNA methylation and early placental growth. Low folate concentrations and no preconceptional intake of folic acid supplements were associated with a smaller first trimester placenta volume, while no associations were found between placental volume and vitamin B12 concentration or paternal age.
Part II of this thesis focusses on the use of a novel technique, Methylated DNA Sequencing (MeD‐seq) to study the genome‐wide maternal cell-free (cfDNA) methylome. First we show that placental DNA methylation markers can be found in maternal cfDNA using MeD-seq, and describe normal changes in cfDNA methylation over gestation in uncomplicated pregnancies. Lastly, we investigate cfDNA methylation differences associated with early-onset preeclampsia (EOPE). After EOPE diagnosis, we show a large increase in total cfDNA, with a relative higher increase in cfDNA fragments from maternal (including endothelium) than placental origin. 
Our studies all reveal that pregnancy‐induced changes in the maternal cfDNA methylome go beyond the additional presence of placental‐originated cfDNA fragments. This underlines the importance of considering the contribution of other tissues to total cfDNA for everyone studying the cfDNA methylome. 
Combined, the studies in part II of this thesis increase our understanding of the largely understudied maternal cfDNA methylome and guide future research.