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.

The intestine plays a crucial role in nutrient digestion and absorption, and its function is critical for animal growth and health. However, the effect of maternal nutrition on offspring’s intestine is not well documented. The objective of this study was to evaluate the effects of maternal supply of polyunsaturated fatty acids, methionine or both during late-gestation on offspring’s intestine amino acids transporters and global DNA methylation. Twenty ewes were used in a randomized block design and treatments were arranged in a 2×2 factorial design. Treatments were: 1) control diet (CTR) without polyunsaturated fatty acids (PUFA) or methionine (MET) supplementation; or supplemented with 2) Ca salts of PUFA (1% DMI; Strata G113®, Virtus Nutrition); rumen-protected MET (0.1% DMI; Smartamine®, Adisseo); and 4) PUFA and MET (PUFA+MET). Treatments were fed from day 100 to 145 of gestation. On day 145, ewes were euthanized and fetuses’ intestines were sampled. Protein quantification of amino acid transporters was measured using Simple Western System and global DNA methylation was determined using a commercial kit. No interactions between PUFA×MET were observed for the variables analyzed. PUFA increased (P ≤ 0.03) global DNA methylation and protein expression of SLC7A5, SLC38A2, and SLC38A10 compared with CTR. Furthermore, PUFA tended to increase (P = 0.07) SLC38A1 protein expression compared with CTR, whereas no difference (P &gt; 0.05) was observed for SLC6A9. Compared with CTR, MET increased (P ≤ 0.05) global DNA methylation and SLC38A10 protein expression, and tented to increase (P ≤ 0.10) SLC6A19 and SLC38A2. MET did not affect SLC7A5 and SLC38A1 compared with CTR. Maternal supply of PUFA and MET led to greater protein expression of amino acid transporters and global DNA methylation on offspring’ intestine; however, the effects of these nutrients were not additive. Further research is necessary to better understand the role of DNA methylation on intestine’s amino acid transporters.

Supplementation with polyunsaturated fatty acids or methionine have a fetal programming effect in mammals. However, the effect of both nutrients on fetal development and DNA methylation have not been explored. The objective of this study was to evaluate the effects of supplementing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), methionine, or both to ewes during late gestation on fetus development and liver global DNA methylation. Twenty ewes (n = 5) were supplemented from day 100 to 145 of gestation. The treatments were: 1) control diet (CONT) without EPA and DHA supplementation (PUFA) or methionine supplementation (MET); 2) control plus PUFA (1 % Ca salts of fatty acids intake, Strata G113®); 3) control plus MET (0.1 % rumen protected methionine intake, Smartamine®); and 4) control plus PUFA and MET (PUFA+MET). On day 145, ewes were euthanized and fetuses were removed. Ewe, fetus, placenta, and fetal liver were weighed. Plasma samples were collected from ewes and fetuses to measure concentration of glucose and NEFA. Liver global DNA methylation was analyzed. Data was analyzed as a complete randomized experiment with a 2x2 factorial arrangement of treatments. Ewe supplementation did not affect (P &gt; 0.1) fetus and placental weight. There was an interaction of treatment effect (P = 0.02) on fetal liver weight and ewe BW; CONT and PUFA+MET were grater that PUFA and MET. There were no differences (P &gt; 0.10) on ewe and fetus NEFA as well as fetus glucose, but MET increased (P = 0.03) ewe plasma glucose concentration. Both treatments affected liver global DNA methylation of fetus (main effects P &lt; 0.01; interaction P = 0.32); all the treatments increased global DNA methylation compared, with CONT, and PUFA+MET has greater than PUFA and MET. In conclusion PUFA and methionine supplementation in late gestation modified fetus liver development and DNA methylation.

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