|Abstract:||During the periparturient period, dairy cows experience major physiological, nutritional, metabolic, and immunological events. Methionine, besides been the first limiting amino, is an important precursor of antioxidants and methyl donor. Therefore, our objective was to examine the effects of enhancing methionine supply on performance, immunometabolic responses, and utero-placental metabolism of dairy cows. Sixty multiparous Holstein cows were used in a block design and assigned to a control diet or the control plus rumen-protected methionine (MET; Mepron, Evonik Nutrition & Care GmbH, Germany). Mepron was fed from −28 to 60 d relative to parturition at a rate of 0.09% and 0.10% of DM during the prepartum and postpartum period, respectively. That rate ensured that the ratio of lysine to methionine in the metabolizable protein was close to 2.8:1. Compared with control, during the fresh period (1-30 days in milk) MET increased intake by 1.7 kg/d, milk yield by 4.1 kg/d, fat yield by 0.17 kg/d, and milk protein yield by 0.20 kg/d. During the high-producing period (31-60 days in milk), cows fed MET increased intake by 1.45 kg/d, milk yield by 4.4 kg/d, fat yield by 0.19 kg/d, and milk protein yield by 0.17 kg/d, compared with control. MET supplementation reduced plasma fatty acids in the fresh period and decreased γ-glutamyl transferase, cholesterol and paraoxonase indicating better liver function. Among the inflammation biomarkers measured, MET led to greater albumin (negative acute-phase protein) and lower haptoglobin than control cows. Cows supplemented with MET had greater plasma concentration of total, β-carotene, tocopherol, and reduced glutathione, whereas reactive oxygen metabolites were lower compared with control cows. Compared with control, MET enhanced blood neutrophil phagocytosis and oxidative burst. Calves from MET-supplemented cows had greater body weight at birth and upregulated mTOR protein expression in the placenta.
Regarding placental nutrient transporters, MET-fed cows had 5 upregulated neutral AA trans-porters (SLC3A2, SLC7A5, SLC38A1, SLC38A2, and SLC38A10). Among the facilitated glucose transporters, MET upregulated the expression of SLC2A1, SLC2A3, and SLC2A4. In MET-fed cows the long-chain fatty acid transporter SLC27A1 and the betaine transporter SLC6A12 were downregulated, while the multivitamin cotransporter SLC5A6 was upregulated. The placentome samples were further analyzed considering the offspring’s sex and maternal treatment. Compared with placenta from Male CTR, Male MET placenta had greater concentrations of end products of the TCA cycle and transsulfuration pathway, and MTR activity. No differences in global DNA methylation or mRNA expression of the DNA methyltransferases were observed between Male CTR and Male MET. Male MET cows delivered heavier calves than Male CTR; however, this difference was not maintained until 9 weeks of age. Female MET placenta compared with Female CTR had greater concentrations of metabolites related to one-carbon metabolism and the TCA cycle. The de no DNA methyltransferase (DNMT3A and DNMT3B) were upregulated in Female MET than Female CTR. Global DNA methylation was lower in Female MET than in Female CTR placenta. No difference in calf birth weight was observed between Female CTR and Female MET; but, calves from Female MET were heavier at 9 weeks of age. Overall, our results indicated that enhancing methionine supply to achieve a lysine:methionine ratio of 2.8:1 during the periparturient period increased animal performance during early lactation, mitigated oxidative stress and inflammation, and enhanced liver and neutrophil function. Furthermore, MET upregulated utero-placental transport of nutrients, at least in part, through the mTOR pathway, and altered placenta metabolism and DNA methylation in a sex-specific way.