Supplementing N-carbamoylglutamate in late gestation increases newborn calf weight by enhanced placental expression of mTOR and angiogenesis factor genes in dairy cows

Abstract

The objective of this study was to investigate whether supplementation with N -carbamoylglutamate (NCG) to cows during late gestation alters uteroplacental tissue nutrient transporters, calf metabolism and newborn weight. Thirty multiparous Chinese Holstein cows were used in a randomized complete block design experiment. During the last 28 d of pregnancy, cows were fed a diet without (CON) or with NCG (20 g/d per cow). The body weight of calves was weighed immediately after birth. Placentome samples were collected at parturition and used to assess mRNA expression of genes involved in transport of arginine, glucose, fatty acid and angiogenesis factors, as well as the mammalian target of rapamycin (mTOR) pathway. Blood samples of calves before colostrum consumption were also collected for the detection of plasma parameters, amino acids (AA) and metabolomics analysis. The newborn weight ( P = 0.02) and plasma Arg concentration of NCG-calves was significantly higher ( P = 0.05) than that of CON-calves, and the plasma concentrations of urea nitrogen tended to be lower ( P = 0.10) in the NCG group. The mRNA abundance of genes involved in glucose transport (solute carrier family 2 member 3 [ SLC2A3 ], P < 0.01), angiogenesis (nitric oxide synthase 3 [ NOS3 ], P = 0.02), and mTOR pathway (serine/threonine-protein kinase 1 [ AKT1 ], P = 0.10; eukaryotic translation initiation factor 4B pseudogene 1 [ EIF4BP1 ], P = 0.08; EIF4EBP2 , P = 0.04; and E74-like factor 2 [ ELF2 ], P = 0.03) was upregulated in the placentome of NCG-supplemented cows. In addition, 17 metabolites were significantly different in the placentome of NCG-supplemented cows compared to non-supplemented cows, and these metabolites are mainly involved in arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and citrate cycle. In summary, the increased body weight of newborn calves from the NCG supplemented dairy cows may be attributed to the increased angiogenesis and uteroplacental nutrient transport and to the activated mTOR signal pathway, which may result in the increased nutrient supply to the fetus, and improved AA metabolism and urea cycle of the fetus.

The Effect of N-Carbamylglutamate Supplementation during the Last Third of Gestation on the Growth and Development of Fetuses Born to Nutrient-Restricted Twin-Bearing Ewes

“…However, supplementation of nutritionally restricted (50% NRC) single-bearing ewes from 100 to 125 dga with Arg also failed to elicit a fetal growth or placental development effect [ 30 ]. In contrast, when animals are fed to meet or exceed nutritional requirements, NCG supplementation during the last 28 dga in cattle [ 22 ], or Arg supplementation from 100 dga to term in twin-bearing ewes [ 10 ], has been reported to have a positive effect on fetal growth. Collectively, these results suggest that the level of nutritional restriction on the ewes in the present study may have been too severe to be rescued by NCG supplementation in mid-late gestation, when the nutritional requirements are the greatest.…”

“…However, the impact on fetal growth and development after 110 days of gestation in sheep has not been reported. One study in dairy cows suggests that maternal supplementation with NCG during the last 28 days of pregnancy improved the newborn weight via improvement of angiogenesis, nutrient transport and urea cycle in the fetus [ 22 ]. It is not clear if a similar time of intervention in pregnant sheep would improve the fetal outcome.…”

The significance of N-carbamoylglutamate in ruminant production

“…Gu et al [ 72 ] reported that dietary supplementation of multiparous Chinese Holstein dairy cows in the last 28 d of gestation increased newborn calf weight by ~ 5 kg which may have been mediated at least in part by enhanced placental expression of mTOR (a key regulator of nutrient transport) and angiogenic factors to enhance nutrient supply to the fetus. Supplementation with NCG from 0–90 d gestation in goats increases circulating Arg concentrations and may improve brown adipose tissue development [ 67 ].…”

High energy diet of beef cows during gestation promoted growth performance of calves by improving placental nutrients transport

“…The fetus exchanges substances with the mother mainly through the placental blood circulation system, obtaining nutrients and excreting metabolic wastes ( 17 ). As the interface between mother and fetus, the placenta can transport important nutrients, such as glucose (GLU), amino acid and fatty acid, from mother to fetus by specific transporters ( 18 ). Higher expressions of nutrient transporters in the placenta are beneficial for nutrients transport, which have important effects on the healthy development of fetus ( 19 ).…”