Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Higher maternal folic acid during gestation dysregulates expression of several genes in mice offspring cerebellum

ABSTRACT: Maternal vitamins and micronutrients during gestational periods have profound impact on the developmemt of newborns as well as influence susceptibility to chronic conditions. Folic acid is indicated to women during pregnancies to prevent occurrence of neural tube defects in infants. Recently, evidence is emerging of the epigenetic effects of folic acid. Since epigenetic changes are crucial in developing fetus, we investigated the effect of maternal higher folic acid supplementation on the gene expression in offspring brains to identify if brain development may be affected. Our results revealed that maternal exposure of higher dose FA diet during gestation dysregulates expression of several genes in the cerebellum of both male and female pups. Dysregulated genes included several transcriptional factors, imprinted genes, neurodevelopmental genes and genes associated with autism spectrum disorder. Adult, 8- to 10-week-old C57BL/6J mice were used in all the experiments and handled according to the protocol reviewed and approved by the Institute for Basic Research Institutional Animal Care and Use Committee. One week prior to mating and throughout the pregnancy two groups of female mice were fed with custom AIN-93G amino acidM-bM-^@M-^Sbased diet (Research Diet, Inc. New-Brunswick, NJ), which contained folic acid (FA) at 2mg/kg and 20 mg/kg diet. At postnatal day one (P1), from FA at 2 mg/kg group: male pupsM-bM-^@M-^Y n=3 and female pupsM-bM-^@M-^Y n=3 were sacrificed by cervical dislocation and cerebellum tissues were collected. From FA at 20 mg/kg group: male pupsM-bM-^@M-^Y n=6 and female pups n=6 were similarly processed. All tissues were snapped frozen and stored at -80M-BM-0C until downstream analysis was performed.

ORGANISM(S): Mus musculus

SUBMITTER: Mohammed Junaid

PROVIDER: E-GEOD-60531 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Objective: Procyanidins are polyphenolic bioactive compounds that exert beneficial effects against obesity and its related diseases. The aim of this study was to evaluate whether the supplementation with low doses of a grape seed procyanidin extract (GSPE) to dams during pre and postnatal periods has biological effects on their offspring at youth. Design: The metabolic imprinting effect of GSPE was evaluated in 30 days-old male offspring of four groups of rats that were fed either a standard diet (STD) or a high-fat diet (HFD) and supplemented with either GSPE at 25 mg per kg of body weight/day or vehicle during pregnancy and lactation. Results: A significant increase in the adiposity index and in the weight of all the white adipose tissue depots studied (retroperitoneal â??RWAT-, mesenteric â??MWAT-, epididymal â??EWAT- and inguinal â??IWAT-) was observed in offspring of dams fed with a HFD and treated with GSPE (HFT group), compared to the offspring of dams fed with the same diet and that do not received procyanidins (HF group). HFT animals also showed a higher number of cells in the EWAT, a sharply decrease of the circulating levels of monocyte chemoattractant protein-1 (MCP-1) as well as a moderate, but significant, decrease of plasma glycerol levels. The transcriptomic analysis performed in the EWAT showed 238 genes differentially expressed between HF and HFT animals, covering an entire range of processes related with the immune function and the inflammatory response (the metabolic pathway mainly reflected in the EWAT), adipose tissue remodeling and function, lipid and glucose homeostasis and metabolism of methyl groups. Conclusion: GSPE treatment to dams fed a HFD during pregnancy and lactation increases adiposity, decreases the circulating levels of MCP-1 and modulates the expression of key genes involved in the adipose tissue metabolism of their offspring. The microarray study was performed with the EWAT RNA samples of rats from the HF and the HFT groups (n=8 animals each).

Project description:Vitamin A (retinol) is an essential precursor for the production of retinoic acid (RA), which in turn is a major regulator of gene expression, affecting cell differentiation throughout the body. Understanding how vitamin A nutritional status, as well as therapeutic retinoid treatment, regulates the expression of retinoid homeostatic genes is important for improving dietary recommendations and therapeutic strategies using retinoids. This study investigated genes central to processes of retinoid uptake and storage, release to plasma, and oxidation in the liver of rats under steady-state conditions after different exposures to dietary vitamin A (deficient, marginal, adequate and supplemented), and acutely after administration of a therapeutic dose of all-trans-RA. Over a very wide range of dietary vitamin A, lecithin:retinol acyltransferase (LRAT) as well as multiple cytochrome P450s (CYP26A1, CYP26B1, and CYP2C22) differed by diet and were highly correlated with one another and with vitamin A status assessed by liver retinol concentration (all correlations, P<0.05). After acute treatment with RA, the same genes were rapidly and concomitantly induced, preceding RARß, a classical direct target of RA. CYP26A1 mRNA exhibited the greatest dynamic range (change of log26 in 3 h). Moreover, CYP26A1 increased more rapidly in the liver of RA-primed rats than naïve rats. By in situ hybridization, CYP26A1 mRNA was strongly regulated within hepatocytes, closely resembling RBP4 in location. Overall, whether RA is produced endogenously from retinol or administered exogenously, changes in retinoid homeostatic gene expression simultaneously favor both retinol esterification and RA oxidation, with CYP26A1 exhibiting the greatest dynamic change. All rats were housed in a room maintained at 22°C with a 12-h dark:light cycle, and food and water were freely available. For the Steady-State Vitamin A Study (experiment 1) and the Retinoic Acid 16-hour Kinetic Study (experiment 2), lactating female Sprague-Dawley rats with 12 female pups (purchased from Charles River Laboratories, Willmington, MA) were fed a vitamin A-deficient purified diet [AIN-93G diet, prepared by Research Diets, New Brunswick, NJ] to reduce the transfer of vitamin A in milk from mother to pups prior to the start of the study. For experiment 1, from weaning, the offspring were fed the same diet modified to contain vitamin A at one of four levels: 0 (vitamin A deficient), 0.4 mg retinol/kg diet (vitamin A marginal), 4 mg retinol/kg diet (vitamin A adequate control), or 100 mg retinol/kg diet (vitamin A supplemented). All rats were studied at 8 weeks of age. Rats were euthanized by carbon dioxide asphyxiation and blood and liver were collected rapidly and frozen in liquid nitrogen for storage at -80°C before analysis. In experiment 2, at 8 weeks of age female vitamin A-deficient rats were treated with ~100 ug of All-trans-Retinoic acid (at-RA) for 0 (vehicle only), 3, 6, 10 or 16 h (n=3-4/group). Tissues were collected and RNA was prepared in the same manner as in experiment 1. In the 90-minute "first pass" kinetic study (experiment 3), female rats were purchased at 6 weeks of age and fed a stock rodent diet. When the rats were 8 weeks old they were assigned to a control (naïve) group. Rats in the naive group received an equal amount of vehicle only (vegetable oil/5% ethanol). Food was removed immediately. Sixteen hours after priming, each rat was lightly anesthetized by isoflurane-oxygen inhalation and treated with ~25 ug all-trans-RA bound to albumin [10 ug RA per 100 g bo dy weight], injected into the exposed left common iliac vein. The incision was closed with a surgical staple. The rats were allowed to recover from the anesthesia. Rats were killed at 0 minute (vehicle injection), and 30, 60, and 90 min (n = 3/group) after injection of the RA test dose. Rats were euthanized by carbon dioxide asphyxiation and blood and liver were collected rapidly and frozen in liquid nitrogen for storage at -80°C before analysis. For experiment 1, five biological repeats were Vitamin A deficient, seven biological repeats were Vitamin A marginal, six biological repeats were Vitamin A adequate, and two biological repeats were Vitamin A supplemented. In experiment 2, three biological repeats were performed for each of the following treatments: untreated, at-RA for 3 hours, at-RA for 6 hours and at-RA for 16 hours. Four biological repeats were treated with at-RA for 10 hours. For experiment 3, two biological repeats were untreated and three biological repeats were performed for each of the following at-RA treatment times: 30, 60 and 90 minutes. A total of 47 samples were analyzed.

Dataset Information

Higher maternal folic acid during gestation dysregulates expression of several genes in mice offspring cerebellum

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure