Maternal N-Carbamylglutamate Supplementation during Early Pregnancy Enhances Embryonic Survival and Development through Modulation of the Endometrial Proteome in Gilts

Zhu, Jinlong; Zeng, Xiangfang; Pan, Qian; Zeng, Shenming; Zhao, Haiyi; Shen, Hexiao; Qiao, Shiyan

doi:10.3945/jn.115.216333

Cited by 21 publications

(23 citation statements)

References 57 publications

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“…The mortality of embryos, fetuses, or newborns was not affected in studies evaluating CIT; however, when NCG was supplemented, this variable decreased in relation to the control group in two studies [40; 41].…”

Section: Resultsmentioning

confidence: 99%

Effectiveness of citrulline and N-carbamoyl glutamate as arginine precursors on reproductive performance in mammals: A systematic review

et al. 2018

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The use of functional nutrients has been proposed to reduce the occurrence of intrauterine growth retardation in animals at birth in several mammalian species. The objective of this study was to verify the effectiveness of citrulline and N-carbamylglutamate (NCG) dietary supplementation as arginine precursors for mammalian species, and the effects on fetal development through a systematic review. The search for studies was performed during August 2018 in the PubMed, ISI Web of Science, Science Direct, and Scopus databases. The literature search was conducted using “arginine precursor”, “citrulline”, or “N-carbamylglutamate” as keywords, combined with “gestation”, “pregnancy”, “fetus”, “newborn”, or “reproduction”. Studies in which arginine precursors were evaluated in gestating mammals and their effects on parameters related to the intrauterine development of the conceptus were selected. Of 1,379 articles, 18 were selected, primarily based on the title and the abstract. Supplementation with NCG (0.5 g to 2 g/kg of feed) increased maternal plasma arginine concentrations in all studies that evaluated this variable. Fetal number increased in 55.56% of the studies that evaluated it, and fetal weight increased in the majority (62.5%) of the studies evaluating this variable. By supplementing citrulline, only fetal weight was improved, with an increase in maternal plasma arginine in 40% of the studies. In conclusion, N-carbamoyl glutamate seems to be an arginine precursor more effective than L-citrulline during gestation; however, both precursors, beside L-Arginine, should be evaluated in similar conditions to confirm the existence of specific particularities such as periods and levels of supplementation, which need to be considered for different species of animals. The supplementation of NCG increases arginine concentrations in maternal plasma, thus improving mammalian reproductive efficiency and fetal development, mainly by promoting higher birth weight.

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Section: Resultsmentioning

confidence: 99%

Effectiveness of citrulline and N-carbamoyl glutamate as arginine precursors on reproductive performance in mammals: A systematic review

et al. 2018

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“…Effect of Prenatal AA in Arginine Family on Maternal Weight Gain and Blood Glucose Levels Gestational weight gain was reported in 23 animal studies (1 mouse [ 33 ], 10 rat [ 36 , 37 , 43 , 44 , 45 , 46 , 49 , 90 , 91 , 148 ], 3 sheep [ 53 , 54 , 55 ], and 9 pig/swine [ 58 , 59 , 66 , 67 , 69 , 74 , 75 , 76 , 149 ]) and only 1 human study (Poland) [ 95 ] ( Table A8 ). Again, the most studied amino acid was arginine ( n = 19) [ 33 , 36 , 37 , 44 , 45 , 46 , 49 , 53 , 54 , 55 , 58 , 59 , 69 , 74 , 75 , 76 , 90 , 91 , 95 ], but also glutamate ( n = 5) [ 54 , 55 , 66 ...…”

Section: Appendix A1 Expanded Methodsmentioning

confidence: 99%

“…Again, the most studied amino acid was arginine ( n = 19) [ 33 , 36 , 37 , 44 , 45 , 46 , 49 , 53 , 54 , 55 , 58 , 59 , 69 , 74 , 75 , 76 , 90 , 91 , 95 ], but also glutamate ( n = 5) [ 54 , 55 , 66 , 148 , 149 ], citrulline ( n = 1) [ 44 ], and glutamine ( n = 1) [ 67 ] were studied. Thirteen studies were conducted in normal-growth pregnancies only [ 33 , 37 , 46 , 58 , 59 , 66 , 67 , 69 , 74 , 75 , 76 , 148 , 149 ], seven were conducted in complicated pregnancies only [ 36 , 44 , 45 , 49 , 53 , 54 , 55 ], three studies had both normal-growth and complicated pregnancy arms […”

Section: Appendix A1 Expanded Methodsmentioning

confidence: 99%

Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis

et al. 2020

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Aberrant fetal growth remains a leading cause of perinatal morbidity and mortality and is associated with a risk of developing non-communicable diseases later in life. We performed a systematic review and meta-analysis combining human and animal studies to assess whether prenatal amino acid (AA) supplementation could be a promising approach to promote healthy fetal growth. PubMed, Embase and Cochrane libraries were searched to identify studies orally supplementing the following AA groups during gestation: (1) arginine family; (2) branched chain (BCAA); (3) methyl donors. Primary outcome was fetal/birth weight. 22 human and 89 animal studies were included in the systematic review. The arginine family, and especially arginine itself, was studied most. Our meta-analysis showed beneficial effects of arginine and (N-Carbamyl) glutamate (NCG), but not aspartic acid and citrulline on fetal/birth weight. However, no effects were reported when isonitrogenous control diet was included. BCAA and methyl donor supplementation did not affect fetal/birth weight. Arginine family supplementation, in particular arginine and NCG, improves fetal growth in complicated pregnancies. BCAA and methyl donor supplementation do not seem to be as promising to target fetal growth. Well controlled research in complicated pregnancies is needed before ruling out AA supplements or preferring arginine above other AAs.

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“…Fat deposition is determined by lipid metabolism. Recent proteomics and metabolomics analyses revealed that NCG supplementation had a significant effect on lipogenesis (13,14) , but the mechanism involved is not clearly understood. Because NCG itself has no other cellular activity beyond activating CPS-I and P5CS (9) , this agent likely exerts its regulatory effect on lipogenesis through altering the synthesis of arginine.…”

mentioning

confidence: 99%

Application of N-carbamylglutamate in Rex rabbits to reduce body fat deposition and its possible mechanism

Wang

Shao

et al. 2020

Br J Nutr

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N-Carbamylglutamate (NCG) has been shown to enhance arginine synthesis and improve growth performance in animals. However, the effect of NCG on body fat deposition remains unknown. This study examined the effects of NCG on body fat deposition and evaluated the potential mechanisms involved. Rex rabbits (3 months old) were assigned to one of four dietary groups and supplemented with NCG at the following different concentrations in a feeding trial that lasted 67 d: 0 (control), 0·04, 0·08, and 0·12 %. NCG supplementation increased serum concentrations of arginine and proline by activating intestinal carbamoylphosphate synthase-І at the posttranscriptional level. Final body weights and growth performance were not affected by dietary NCG levels. However, NCG-treated rabbits had lower perirenal and subcutaneous fat percentages, serum TAG content, and hepatic fatty acid synthase (FAS) activity and increased NO synthase activity and serum levels of NO, growth hormone (GH), and insulin-like growth factor 1 (IGF-1). There were significant positive correlations between TAG content and perirenal fat percentage, as well as FAS activity and perirenal fat percentage, but significant negative correlations between TAG and NO levels, and FAS activity and IGF-1 level in rabbits after NCG treatment. NCG supplementation did not affect hepatic health indicators, except for serum ammonia concentrations, which were decreased in NCG-treated rabbits. Our results suggest that NCG can serve as a dietary supplement to reduce unfavourable fat deposition through inhibiting hepatic lipogenesis in animals since it appears to have no negative effects on growth performance or hepatic health.

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Maternal N-Carbamylglutamate Supplementation during Early Pregnancy Enhances Embryonic Survival and Development through Modulation of the Endometrial Proteome in Gilts

Abstract: To our knowledge, our results provide the first evidence that altered abundance of the endometrial proteome induced by NCG supplementation is highly associated with the improvement of embryonic survival and development in gilts.

Cited by 21 publications

References 57 publications

Effectiveness of citrulline and N-carbamoyl glutamate as arginine precursors on reproductive performance in mammals: A systematic review

Effectiveness of citrulline and N-carbamoyl glutamate as arginine precursors on reproductive performance in mammals: A systematic review

Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis

Application of N-carbamylglutamate in Rex rabbits to reduce body fat deposition and its possible mechanism

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