Endocrine Abstracts

Almost 2 billion adults in the world are overweight, and obesity linked metabolic disorders are a worldwide health concern affecting about one-third women of reproductive age. Obesity during pregnancy can increase the risk of complications for both mother and the baby leading to risk of metabolic diseases by programming in utero events. Vitamin B12 (B12) has a potential epigenetic role that could influence placental dysfunction and fetal metabolism. Here, we aim to identify epigenetically regulated genes and miRNAs due to B12 deficiency through comprehensive integrated multi-omics on placenta. We integrated differentially methylated regions (from RRBS-seq), differentially expressed genes (from RNA-seq) and differentially expressed miRNAs (from sRNA-seq) in placental tissues (n = 50) from pregnant women (PRiDE cohort) with deficient (<220 pmol/l) and sufficient (>220 pmol/l) levels of B12 adjusting for clinical covariates including maternal age, fetal sex and body mass index. The study identified 2,565 hypomethylated and 2,792 hypermethylated regions in gene promoters associated with B12 deficiency. Furthermore, 270 and 46 differentially expressed genes and miRNAs were identified respectively. Integrative analysis of differentially methylated regions, differentially expressed genes and miRNAs revealed 13 genes (GYPC, NTRK2, EVA1C, DMTN, PRLHR, HYAL1, ZBTB16, PMIS2, CGB5, LYPD3, LHX3, FAM167A, FTCD) and 11 miRNAs (mir-373, miR-3940, miR-5708, miR-1299, miR-18b, miR-219b, miR-3667, miR-4664, miR-4784, miR-5683, miR-6859) due to B12 deficiency during pregnancy. Further enrichment analysis identified glycosaminoglycan degradation, one carbon pool by folate and histidine metabolism as the top deregulated pathways. These findings potentially can unravel the molecular mechanisms associated with maternal B12 deficiency in placenta. This study also highlights the significance of integrative multi-omics approach for in-depth characterisation of epigenomic and transcriptomic signatures in human placenta associated with metabolic risks.