Maternal Energetics, Placental Epigenetics, and Developmental Programming
thesisposted on 2017-10-27, 00:00 authored by Stephanie Laren Riesche
The purpose of this dissertation was to integrate well-established aspects of the marmoset monkey with innovative DNA methylation (DNAm) methodologies (i.e. reduced representation bisulphite sequencing) to gain insight about the role of placental DNAm in a valuable model of developmental programming of obesity. The introduction lays the theoretical and conceptual groundwork and is followed by two independent, but complementary papers. The aim of the first paper, The Common Marmoset Monkey: Avenues for Exploring Prenatal and Placental Mechanisms in Developmental Programming of Pediatric Obesity, was to position the marmoset monkey as a sophisticated model for exploring the maternal and placental mechanisms involved in developmental programming of obesity. The two aims of the second paper, DNA Methylation in the Marmoset Monkey: Maternal weight epigenetically affects genes involved in metabolic pathways, were (1) to describe placental DNAm for the first time in this species; and (2) to explore the association between maternal metabolic health and DNAm of genes and gene pathways in the placenta. To the best of our knowledge, this is the first study to report genome-wide placental DNAm in the common marmoset monkey. Importantly, these results were obtained in an animal model with a high degree of biological salience for translational research. The findings from the primary aim of the second paper establishing DNAm patterns in the marmoset placenta provide a valuable step in developing the marmoset monkey as model of investigating the role of placental epigenetics in developmental programming. The secondary aim of paper two was to begin to understand the impact of maternal metabolic status on placental DNAm at the epigenome-wide level by identifying genes and gene pathways that are affected by maternal weight during gestation. One of the principal findings of this aim was that maternal weight is associated with DNAm in genes that are predominantly involved in energy metabolism and homeostasis such as the regulation of glycolytic processes (GO:0006110), and the regulation of lipid metabolic processes pathways (GO:0019216). Combined, the findings of this study establish the marmoset as a model worthy of exploring placental epigenetic contributions to developmental programming and reinforce the growing body of evidence that demonstrate the effects of maternal metabolic status on placental DNAm.