Methionine Supply During Late-Gestation Triggers Offspring Sex-Specific Divergent Changes in Metabolic and Epigenetic Signatures in Bovine Placenta.

Background: Nonruminant male and female offspring respond differently to gestational nutrition, with placenta contributing to the underlying mechanisms. However, similar data are lacking in large ruminants. Objectives: The aim of this study was to investigate the impact of methionine supply during late-gestation on metabolism and DNA methylation in placenta from cows carrying male or female calves. Methods: During the last 28 d of pregnancy, cows were individually fed a control diet (CON) or the control diet plus rumen-protected d,l-methionine (MET; 0.9 g/kg dry matter intake). Placentomes collected at term were classified according to cow dietary treatment and offspring sex as follows: Male CON (n = 7), Male MET (n = 7), Female CON (n = 8), and Female MET (n = 8). Calf growth was measured until 9 wk of age. Targeted metabolomics, RT-PCR, global DNA methylation, and activity of selected enzymes in one-carbon metabolism and transsulfuration pathways were performed. Statistics were conducted via ANOVA using MIXED models. Results: At birth, Male MET calves were heavier than Male CON calves (7.6%, P = 0.02), but body mass was similar at 9 wk of age. In contrast, compared with Female CON, Female MET calves had greater body mass at 9 wk of age (6.3%, P = 0.03). Compared with Male CON, placenta from Male MET calves had greater concentrations of tricarboxylic acid (TCA) cycle and transsulfuration intermediates (23-100%, P < 0.05), along with greater 5-methyltetrahydrofolatehomocysteine methyltransferase activity (67%, P = 0.03). Compared with Female CON, placenta from Female MET calves had greater concentrations of one-carbon metabolism intermediates (13-52%, P < 0.05). DNA methyltransferase 3A (DNMT3A) was upregulated (43%, P < 0.01) in placenta from Female MET compared with Female CON calves. Global DNA methylation was lower in placenta from Female MET compared with Female CON calves (45%, P = 0.06). Conclusions: Methionine supply affects placental metabolism, DNA methylation, and body mass of the calf in a sex-specific manner, underscoring its importance as dietary methyl-donor for pregnant cows.

Hepatic Cystathionine ß-Synthase Activity Is Increased by Greater Postruminal Supply of Met during the Periparturient Period in Dairy Cows.

BACKGROUND: Postruminal supply of Met during the periparturient period enhances production efficiency (feed conversion to milk) in dairy cows partly through alleviation of oxidant and inflammatory status. Whether alterations in hepatic 1-carbon metabolism (major contributor of antioxidants) and/or energy metabolism contribute to these beneficial effects is unknown. OBJECTIVES: To investigate alterations in hepatic 1-carbon and energy metabolism and associations with plasma amino acids (AAs) and production efficiency in response to enhanced postruminal supply of Met. METHODS: Holstein cows (n = 30 per group) were fed during the last 28 d of pregnancy a control diet (CON) or the control plus ethylcellulose rumen-protected Met (MET; 0.9 g/kg of dry matter intake). Plasma (n = 15 per group) and liver tissue (n = 10 per group) were collected throughout the periparturient period to evaluate AA profiles, activity of the tricarboxylic acid cycle, and 1-carbon metabolism via mRNA abundance, enzyme activity, and targeted metabolomics. RESULTS: Cows in the MET group had greater overall (27%, P = 0.027) plasma Met concentrations, but had similar total plasma AA concentrations. Although mRNA abundance of 1-carbon metabolism enzymes did not differ, hepatic activity of cystathionine ß-synthase (CBS) (51.2 compared with 44.4 mmol/h/mg protein; P = 0.032) and concentration (19%, P = 0.048) of the cellular antioxidant glutathione were greater overall in the MET group. mRNA abundance of aconitase 2 and fumarate hydratase was greater overall (P = 0.049), and phosphoenolpyruvate carboxykinase 1 tended (P = 0.093) to be greater overall in cows fed MET. There was a tendency (P ≤ 0.093) for greater overall hepatic concentrations of malic acid, α-ketoglutaric acid, and isocitric acid in cows fed MET. CONCLUSIONS: Greater activity of CBS in response to enhanced postruminal supply of Met likely contributes to alleviating oxidant status by increasing concentrations of glutathione. Hence, transsulfuration plays an important role in the observed improvements in production efficiency of dairy cows during the periparturient period.