Metabolomics profile of umbilical cord blood is associated with maternal pre-pregnant obesity in a perspective multi-ethnic cohort displaying health disparities
Project description:Maternal obesity is becoming a major health consideration for successful pregnancy outcomes. There is growing proof that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are so far poorly understood. We set out to analyse term placenta whole transcriptome in obese (n=5) and normoweight women (n=5), using Affymetrix microarray platform compromising of 50,000 probe sets. Our analysis shows that the placental transcriptome differs between normoweight and obese women. Different processes and pathways among placenta from obese women were dysregulated, including inflammation and immune responses, lipid metabolism, cell death and survival and cancer pathways, vasculogenesis and angiogenesis, and glucocorticoid receptor signaling pathway. Together, this global gene expression profiling approach demonstrates and confirms that maternal obesity creates a unique in utero environment that impairs placental transcriptome.
Project description:Maternal obesity is a health concern that may predispose newborns to a high risk of medical problems later in life. To understand the transgenerational effect of maternal obesity, we conducted a multi-omics study, using DNA methylation and gene expression in the CD34+/CD38-/Lin- umbilical cord blood hematopoietic stem cells (uHSCs) and metabolomics of the cord blood, all from a multi-ethnic cohort (n=72) from Kapiolani Medical Center for Women and Children in Honolulu, Hawaii (collected between 2016 and 2018). Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.05), adjusting for major clinical confounders. Functional analysis revealed significant associations of differentially methylated sites with downregulated cell cycle, lipid synthesis, immune signaling, and metabolic pathways. Utilizing Shannon entropy to evaluate uHSCs methylation levels, we discerned a notable impact of maternal obesity on higher quiescence of uHSCs. Further, the multi-omics integration revealed dysfunction in adipogenesis, erythropoietin production, cell differentiation and DNA repair. This study reveals a significant correlation between pre-pregnancy maternal obesity and multi-omics level molecular changes in the uHSCs of offspring, particularly in DNA methylation. These findings suggest that maternal obesity can lead to alterations that affect physiological pathways in the offspring.