Effects of maternal dietary omega-3 polyunsaturated fatty acids and methionine during late gestation on fetal growth, DNA methylation, and mRNA relative expression of genes associated with the inflammatory response, lipid metabolism and DNA methylation in placenta and offspring's liver in sheep

母体妊娠晚期膳食中ω-3多不饱和脂肪酸和蛋氨酸对绵羊胎盘和子代肝脏中胎儿生长、DNA甲基化以及与炎症反应、脂质代谢和DNA甲基化相关的基因mRNA相对表达的影响

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Abstract

BACKGROUND: Omega-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. RESULTS: A 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. CONCLUSION: Omega-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.

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