Background and Objectives: Offspring born to obese mothers are at an increased risk of chronic disease including type 2 diabetes (T2D), obesity, hypertension, cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This metabolic programming is produced, in part, by epigenetic changes such us DNA methylation. We postulated that obesity exposure impacts the offspring's methylome and used an epigenomic approach to explore this hypothesis in placenta and umbilical cord.
Methods: Placenta and umbilical cord samples were obtained from 24 mother-newborns pairs [8 with pregestational obesity and increased gestational weight gain (OB-OB), 8 with pregestational normal weight and increased gestational weight gain (Norm-OB) and 8 with pregestational normal weight and normal gestational weight gain (Norm-Norm). Women were recruited at the first trimester of pregnancy and followed until delivery. DNA methylation was measured at >850 000 CpG sites (Infinium® MethylationEPIC BeadChip). The association between the methylation status and maternal obesity was studied using beta regression models (with pregestational BMI as predictor and the methylation level of each CpG as response). DAVID bioinformatic analysis was conducted to study the possible functional roles of the differentially methylated genes (identification of significant metabolic pathways and potentially affected diseases/disorders).
Results: In all the study subjects pooled together in a group, pregestational BMI associated with the differential methylation of 1,031 CpG sites (742 genes) and 369 CpG sites (314 genes) in placenta and umbilical cord, respectively [false discovert rate (FDR)-corrected P-value<0.05). The differentially methylated gens in the placenta were involved in pathways related to cell growth and proliferation (MAPK, cGMP and cAMP) and had potential effect on metabolic disorders such as T2D, coronary heart disease and glycosylated hemoglobin (all P<0.05). The differentially methylated genes in the umbilical cord were involved in pathways related to cell proliferation and lipid metabolism (AMPk, FoxO, lipolysis, mTOR) and had a potential effect on metabolic diseases such as T2D, obesity and hypertension (all P<0.05).
Conclusions: Our results show that pregestational obesity may cause epigenetic alterations (DNA methylation) in placenta and umbilical cord genes involved in fetal growth and development, which may have potential effects on metabolic disorders. Perinatal epigenetic analyses may thus have utility in identifying individual vulnerability to later metabolic diseases.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology