Project description:It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver methylome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. Modifications of DNA methylation were found in the promoter regions of 1,032 genes out of 14,981 genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function. MDD induced modifications of methylation in rat liver were measured in 21-day-old rats born to dams fed with standard food or food deficient in methyl group donor. Six independent experiments were performed (3 controls versus 3 MDD).
Project description:It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver transcriptome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. From a total of 44,000 probes for 26,456 genes, we found two gene clusters whose expression levels had statistically significant differences between control and deficient rats: 3,269 up-regulated and 2,841 down-regulated genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function. Modifications of gene expression in rat liver were measured in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates). Eight independent experiments were performed (4 Controls versus 4 Methyl Donor Deficiency - MDD).
Project description:The aim of this study was to evaluate the potential effects of methyl donor supplementation of pregnant animals in the presence or absence of a concomitant lactation on the methylome of the offspring. Twenty Holstein cows, 10 nulliparous (not lactating while pregnant) and 10 multiparous (lactating while pregnant) were blocked by parity and randomly assigned to an i.m. weekly injections of a placebo (CTRL) or a solution containing methyl donors (MET). After calving, 5 calves randomly selected from each treatment (two born to primiparous and three to multiparous dams) were blood-sampled to determine their full methylome. There were more than 2,000 CpG differentially methylated between calves born to CTRL and those born to MET, and also between calves born to multiparous and nulliparous dams. Most of the differences affected genes involved in immune function, cell growth regulation and differentiation, kinase activity, and ion channeling. We conclude that the coexistence of pregnancy and lactation affects the methylome of the offspring, and that supplementation of methyl donors early in gestation has also consequences on the methylome.
Project description:The study objective was to determine differentially expressed mRNA transcripts in cardiac tissues from E18.5 fetal mice e born to obese dams fed a high fat/high sugar diet and control dams fed normal diet.
Project description:The transcriptional profile of liver samples from male C57BL/6J mice was evaluated using a dual-channel microarray. The mice were divided into two groups: a negative control group fed a high-fat diet, and an experimental group fed a high-fat diet supplemented with methyl donors. This approach allowed for the analysis of gene expression differences associated with methyl donor supplementation in the context of a high-fat diet.
Project description:Early methyl donor –especially B9 and B12 vitamins- deficiency (MDD) is involved in birth defects and brain development retardation. Molecular mechanisms that take place in response to MDD still remain not well understood. In this study we took advantage of a rat nutritional MDD model and performed a microarray analysis on female cerebellum, in order to identify which genes and molecular pathways are disrupted in response to MDD. We found that cerebellum development is altered, with a decrease of the granular cell layer thickness in cerebellum at P21. Furthermore, we investigated the involvement of Wnt-signaling pathway –a major molecular pathway involved in neuronal development but also later in synaptic assembly and neurotransmission. We found that Wnt canonical and Ca2+ pathways are disrupted following early MDD. Notably, we identified GSK3β as a pivotal player affected by MDD, affecting synaptic assembly and signaling. These results could explain the structural brain defects previously observed in response to early MDD and identify new genes and a new molecular pathway that is affected following nutritional methyl donor deprivation.
Project description:A comparison of the liver transcriptomes of 1 day old rats that are born to mothers fed with three different diets during gestation. The first animal group was fed with a normal diet (control); second group received much less protein than normal and slightly more carbs (low protein); third group diet was same as low protein but with an extra dosage of folic acid (lowp.+f). All diets were matched for energy. Total RNA was extracted from rat livers of 4 offsprings per animal group (4 biological replicates x group)
Project description:We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. Experiment Overall Design: In the current study, rat pups (with their dams) were exposed to hypoxia from birth and compared to pups from normoxic dams fed ad libitum. Adrenal glands were collected from normoxic and hypoxic pups at PD7and pooled (N=24/sample; 4 samples per treatment group) for total RNA extraction. Microarray analysis was performed, followed by verification with real-time PCR. Furthermore, the expression of selected genes involved in adrenal function was analyzed by real-time PCR, regardless of microarray results.