Abstract
BackgroundOmega-3 PUFA or methionine (Met) supply during gestation alters offspring physiology. However, the effect of both nutrients on fetal development has not been explored. Our objective was to determine the effects of supplementation of these two nutrients during late gestation on fetal growth, DNA methylation, and mRNA expression of genes associated with the inflammatory response, and DNA methylation. Ewes (n = 5/treatment) were fed from day 100 to 145 of gestation one of the following treatments: 1) basal diet (NS) without fatty acids (FS) or methionine (MS) supplementation; 2) FS (10 g/kg Ca salts, source omega-3 PUFA); 3) MS (1 g/kg rumen protected methionine); and 4) FS and MS (FS-MS). On day 145, ewes were euthanized, and data from dams and fetus was recorded. Placenta (cotyledon), fetal liver, and blood samples were collected.ResultsA treatments interaction on fetal liver weight, ewe body weight and body condition score (BCS) was observed; FS-MS were heavier (P < 0.01) than FS and MS, and FS-MS ewes had a better (P = 0.02) BCS than NS. Methionine increased (P = 0.03) ewe plasma glucose concentration. Fetal liver global DNA methylation increased (P < 0.01) in FS and MS. Dietary treatments modify the mRNA relative expression on some of the genes evaluated. In the fetal liver, FS increased (P = 0.04) the mRNA relative expression of arachidonate-5-lipoxygenase-activating-protein and tended to decrease (P = 0.06) methionine-adenosyltransferase-1A. Moreover, MS decreased (P = 0.04) DNA-methyltransferase-1 and tended to decrease (P = 0.08) free-fatty-acid-receptor-1 mRNA relative expression. Furthermore, FS-MS decreased mRNA relative expression of tumor-necrosis-factor-alpha (P = 0.05), peroxisome-proliferator-activated-receptor-delta (P = 0.03) and gamma (P = 0.04), tended to decrease (P ≤ 0.09) interleukin-6, fatty-acid-transport-protein-1, and delta-5-desaturase, and increased adenosylhomocysteinase (P = 0.04) mRNA relative expression. In cotyledon, FS tended to decrease fatty acid binding protein 4 (P = 0.09) mRNA relative expression.ConclusionOmega-3 PUFA and Met supplementation improves dam’s performance in late gestation, which was positively correlated with an increase in offspring’s liver development. Moreover, FS-MS decreased mRNA relative expression of proinflammatory cytokines, and lipogenic genes, and increased the expression on an enzyme that has an important role in methylation.
Highlights
Omega-3 polyunsaturated fatty acids (PUFA) or methionine (Met) supply during gestation alters offspring physiology
Ewes were blocked by age and Body weight (BW); and within each block randomly assigned to one of four treatments (5 pens per treatment): 1) A basal diet was fed to meet pregnant ewe nutrient requirements during late gestation [26], 2) Basal diet plus a source omega-3 PUFA (FS; 10.1 g/kg dry matter intake [Dry matter intake (DMI)] with Ca salts of Fatty acid (FA) [Strata G113, Virtus Nutrition]), 3) Basal diet plus Met (MS; 1.0 g/kg DMI with rumen protected Met [Rumen protected methionine (RPM), Smartamine® M, Adisseo]), and 4) Basal diet plus omega-3 PUFA and Met (FS-Methionine supplementation (MS); same doses and sources listed for the Fatty acids supplementation (FS) and MS treatments)
According to previous studies [4, 11, 28], we expect that fetus growth from dams supplemented with these two nutrients will be associated with an increase in the mRNA expression of the enzymes that participates in DNA methylation (DNMT), Met cycle, and resolvin D1 (RvD1) metabolic pathway after PUFA supplementation
Summary
Omega-3 PUFA or methionine (Met) supply during gestation alters offspring physiology. Our objective was to determine the effects of supplementation of these two nutrients during late gestation on fetal growth, DNA methylation, and mRNA expression of genes associated with the inflammatory response, and DNA methylation. Changes in offspring’s growth and physiology after maternal supply of omega-3 polyunsaturated fatty acids (PUFA) or methionine (Met) during late gestation has been associated with alterations in gene expression [3, 4]. One of the genes affected by the omega-3 PUFA supplementation was the DNAmethyltransferase (DNMT)-3A [11], an enzyme that methylate DNA Another gene in the cotyledon affected by maternal supply of omega-3 PUFA was free fatty acid receptor (FFAR)-4 [11], a gene involved in lipid metabolism. Supplementation with omega-3 PUFA enhanced resolvins basal concentrations [18,19,20], and increased the mRNA expression of lipoxygenases (ALOX), enzymes that synthetized resolvin D1 (RvD1) [19]
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