52 Young Scholar Presentation: Maternal supply of methionine during late-pregnancy alters in utero and neonatal development, hepatic one-carbon metabolism,and innate immune response in Holstein calves

Abstract

Abstract Pregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition. Objectives were to investigate if increasing methionine (Met) supply during late-pregnancy affects developmental, metabolic, and immune parameters of the calf at birth and during the neonatal period. Calves born to Holstein cows individually-fed a basal control (CON; 1.47 Mcal/kg dry matter [DM] and 15.3% crude protein) diet with no added Met or CON plus rumen-protected Met (MET; Mepron® at 0.09% of diet DM) during the last 28±2 d of pregnancy were used. Liver biopsies were harvested at 4, 14, 28, and 50 d of age and used for metabolomics via GS-MS and activity of hepatic 1-carbon metabolism enzymes. Blood for biomarker analyses and innate immune function assays was harvested at birth (before colostrum feeding), 7, 21, 42 and 50 d of age. Whole blood was challenged with enteropathogenic bacteria (E. coli 0118:H8), and phagocytosis and oxidative burst of neutrophils and monocytes quantified by flow cytometry. At birth, MET calves had greater (P≤0.05) body weight (BW, 44.1 vs. 42.1±0.70 kg), hip height (HH, 81.3 vs. 79.6±0.53 cm), and wither height (WH, 77.8 vs. 75.9±0.47 cm). Differences persisted through 9 wk of age, resulting in average responses of +3.1 kg BW, +1.9 cm HH, and+1.8 cm WH in MET compared with CON. Average daily gain during the 9 wk was (P<0.05) 0.72±0.02 kg/d in MET and 0.67±0.02 kg/d in CON calves. Despite similar rates of daily DMI, maternal supplementation with Met led to greater (P ≤ 0.05) overall hepatic concentrations of the 1-carbon metabolism intermediates adenosine, betaine, choline, glycine, and N,N-dimethylglycine in liver tissue. Among transsulfuration pathway metabolites, concentrations of cystathionine, cysteinesulfinic acid, hypotaurine, serine, and taurine were greater (P ≤ 0.05) in MET calves. There was a treatment × day effect for activity of betaine-homocysteine S-methyltransferase (BHMT), methionine synthase (MTR) and cystathionine-beta-synthase (CBS) in liver tissue. Activity of BHMT and CBS increased in MET calves between d 4 and 14, with a peak at 28 d. Despite a linear increase from d 4 to 28, activity of MTR in MET calves was lower on d 4 and 50. Plasma concentrations of haptoglobin and activity of myeloperoxidase in both maternal groups increased (P ≤ 0.05) markedly between 0 and 7 d of age followed by a decrease to baseline at d 21 with responses being lower in MET compared with CON calves. In vitro phagocytosis in stimulated neutrophils was greater overall (P ≤ 0.05) in MET calves. Overall, data indicate that increasing the maternal supply of Met during late-pregnancy benefits calf growth in part through alterations in hepatic metabolism and innate immune response.