<i>L</i>-citrulline and <i>L</i>-arginine improve reproductive performance in primiparous and multiparous cows via distinct shared metabolic pathways and pyrimidine metabolism.

抄録

Background: To investigate the impact of L-arginine (L-Arg) and L-citrulline (L-Cit) on cow reproductive performance.Methods: 90 healthy, age-matched Simmental cows were randomly assigned to three groups: control, L-Arg, and L-Cit, with 30 cows per group. Estrus synchronization was performed, and various parameters were assessed, including estrus rate, conception rate, and early embryo apoptosis, following intraperitoneal administration of L-Arg and L-Cit. Additionally, reproductive hormones, serum antioxidant levels, and plasma metabolites were measured.Results: Results indicated that both the estrus and conception rates in the L-Arg and L-Cit groups were significantly higher than those in the control group (p < 0.05). Furthermore, serum LH levels and VEGF concentrations on day 1 and day 8 were elevated in the L-Arg and L-Cit groups compared to controls (p < 0.05). Estrus rate and serum NO concentration in the L-Cit group were notably higher than those in the control group (p < 0.05). At day 8 and day 21, estrus rate, conception rate, P levels, and serum VEGF concentrations were significantly greater in both the L-Arg and L-Cit groups compared to controls (p < 0.05). Additionally, serum NO concentration was significantly higher in the L-Cit group than in the control group (p < 0.05). The activities of T-AOC and GSH-Px in serum were significantly increased in both primiparous and multiparous cows in the L-Arg and L-Cit groups relative to the control group (p < 0.05). Metabolomic analysis revealed that in primiparous cows, the protein digestion and absorption, ABC transporters, and AMPK signaling pathways were significantly enriched. In multiparous cows, pyrimidine metabolism was notably enriched.Conclusion: Under the experimental conditions, L-Arg modulated the production of Dimethyl sulfone, 1,5-pentanediamine, Bassanolide, and Phenylalanine in primiparous cows through the protein digestion and absorption and ABC transporters pathways, while L-Cit influenced the same metabolites via the ABC transporters pathway. Both L-Arg and L-Cit promoted increased NO, GSH-Px, T-AOC, and VEGF levels, enhancing early embryo implantation. Additionally, L-Arg and L-Cit synergistically influenced pyrimidine metabolism, regulating the production of N-myristoylphosphorylcholine, N-oleoyl-d-erythro-sphingosylphosphorylcholine, 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, and 1-docosahexaenoyl- 2-stearoyl-sn-glycero-3-phosphocholine. This modulation resulted in increased NO, GSH-Px, T-AOC, and VEGF in multiparous cows, ultimately supporting early embryo implantation.