3 years ago

Maternal vitamin B 12 deficiency in rats alters DNA methylation in metabolically important genes in their offspring

Vinay Singh Tanwar, Sourav Ghosh, Satish Sati, Subhoshree Ghose, Lovejeet Kaur, Kalle Anand Kumar, K. V. Shamsudheen, Ashok Patowary, Meghna Singh, V. Jyothi, Pujitha Kommineni, Sridhar Sivasubbu, Vinod Scaria, Manchala Raghunath, Rakesh Mishra, Giriraj Ratan Chandak, Shantanu Sengupta
Vitamin B12 deficiency is a critical problem worldwide and peri-conceptional deficiency of this vitamin is associated with the risk of complex cardio-metabolic diseases. Nutritional perturbations during these stages of development may lead to changes in the fetal epigenome. Using Wistar rat model system, we have earlier shown that low maternal B12 levels are associated with low birth weight, adiposity, insulin resistance, and increased triglyceride levels in the offspring, which might predispose them to the risk of cardio-metabolic diseases in adulthood. In this study, we have investigated the effects of maternal B12 deficiency on genome-wide DNA methylation profile of the offspring and the effect of rehabilitation of mothers with B12 at conception. We have performed methylated DNA immunoprecipitation sequencing of liver from pups in four groups of Wistar rats: Control (C), B12-restricted (B12R), B12-rehabilitated at conception (B12RC), and B12-rehabilitated at parturition (B12RP). We have analyzed differentially methylated signatures between the three groups as compared to controls. We have identified a total of 214 hypermethylated and 142 hypomethylated regions in the 10 kb upstream region of transcription start site in pups of B12-deficient mothers, which are enriched in genes involved in fatty acid metabolism and mitochondrial transport/metabolism. B12 rehabilitation at conception and parturition is responsible for reversal of methylation status of many of these regions to control levels suggesting a causal association with metabolic phenotypes. Thus, maternal B12 restriction alters DNA methylation of genes involved in important metabolic processes and influences the offspring phenotype, which is reversed by B12 rehabilitation of mothers at conception.

Publisher URL: http://link.springer.com/article/10.1007/s11010-020-03713-x

DOI: 10.1007/s11010-020-03713-x

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