Dietary N-carbamylglutamate and rumen-protected L-arginine supplementation during intrauterine growth restriction in undernourished ewes improve fetal thymus development and immune function.

The aims of the present study were to determine whether dietary supplementation with N-carbamylglutamate (NCG) and rumen-protected l-arginine (RP-Arg) to underfed Hu sheep would improve fetal thymus development and immune function. From Day 35 to Day 110 of gestation, 32 Hu ewes carrying twin fetuses were randomly allocated to one of four groups (n=8 per group): 100% National Research Council (NRC)-recommended nutrient requirements (CON), 50% NRC recommendations (RES), 50% NRC recommendations supplemented with 20gday-1 RP-Arg (RES+ARG), and 50% NRC recommendations supplemented with 5gday-1 NCG (RES+NCG). Medullary thickness was increased (P<0.05) in RES compared with CON ewes, but was reduced (P<0.05) in both RES+ARG and RES+NCG ewes compared with RES ewes. There were no differences in superoxide dismutase and glutathione peroxidase activity or malondialdehyde levels in the RES+ARG and RES+NCG groups compared with the CON group (P>0.05). Concentrations of IgA, interleukin (IL)-1ß and IL-10 in fetal umbilical cord blood were reduced (P<0.05) in RES compared with CON ewes, but were increased (P<0.05) in both RES+ARG and RES+NCG ewes. Expression of Bax, Fas and p53 mRNA was increased (P<0.05) in RES compared with CON ewes, but were reduced (P>0.05) in both RES+ARG and RES+NCG ewes. These results indicate that dietary supplementation with NCG and RP-Arg could help alleviate the negative effects of intrauterine growth restriction on fetal thymus development and immune function.

N-carbamylglutamate and L-arginine improved maternal and placental development in underfed ewes.

The objectives of this study were to determine how dietary supplementation of N-carbamylglutamate (NCG) and rumen-protected L-arginine (RP-Arg) in nutrient-restricted pregnant Hu sheep would affect (1) maternal endocrine status; (2) maternal, fetal, and placental antioxidation capability; and (3) placental development. From day 35 to day 110 of gestation, 32 Hu ewes carrying twin fetuses were allocated randomly into four groups: 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations, 50% of NRC recommendations supplemented with 20g/day RP-Arg, and 50% of NRC recommendations supplemented with 5g/day NCG product. The results showed that in maternal and fetal plasma and placentomes, the activities of total antioxidant capacity and superoxide dismutase were increased (P<0.05); however, the activity of glutathione peroxidase and the concentration of maleic dialdehyde were decreased (P<0.05) in both NCG- and RP-Arg-treated underfed ewes. The mRNA expression of vascular endothelial growth factor and Fms-like tyrosine kinase 1 was increased (P<0.05) in 50% NRC ewes than in 100% NRC ewes, and had no effect (P>0.05) in both NCG- and RP-Arg-treated underfed ewes. A supplement of RP-Arg and NCG reduced (P<0.05) the concentrations of progesterone, cortisol, and estradiol-17ß; had no effect on T4/T3; and improved (P<0.05) the concentrations of leptin, insulin-like growth factor 1, tri-iodothyronine (T3), and thyroxine (T4) in serum from underfed ewes. These results indicate that dietary supplementation of NCG and RP-Arg in underfed ewes could influence maternal endocrine status, improve the maternal-fetal-placental antioxidation capability, and promote fetal and placental development during early-to-late gestation.