Amino Acids

, Volume 45, Issue 3, pp 479–488 | Cite as

Dietary l-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus

  • Wenkai Ren
  • Wei Luo
  • Miaomiao Wu
  • Gang Liu
  • Xinglong Yu
  • Jun Fang
  • Teijun Li
  • Yulong Yin
  • Guoyao Wu
Original Article


Porcine circovirus type 2 (PCV2) causes reproductive failure in swine. As glutamine can enhance immune function in animals, this study was conducted with mice to test the hypothesis that dietary glutamine supplementation will improve pregnancy outcome in PCV2-infected dams. Beginning on day 0 of gestation, mice were fed a standard diet supplemented with 1.0% l-glutamine or 1.22% l-alanine (isonitrogenous control). All mice were infected with PCV2 (2000 TCID50) on day 10 of gestation. On day 17 of gestation, six mice from each group were euthanized to obtain maternal tissues and fetuses for hematology and histopathology tests. The remaining mice continued to receive their respective diets supplemented with 1.0% l-glutamine or 1.22% l-alanine through lactation. The PCV2 virus was present in maternal samples (serum and lung) of most mice in the control group but was not detected in the glutamine-supplemented mice. Dietary glutamine supplementation reduced abortion, decreased fetal deaths, and enhanced neonatal survival. The glutamine treatment also reduced concentrations of interleukin-6, while increasing concentrations of tumor necrosis factor-α and C-reactive protein, in the maternal serum of mice. Furthermore, glutamine supplementation attenuated microscopic lesions in maternal tissues (lung, spleen, and liver). Collectively, these results indicate that dietary glutamine supplementation is beneficial for ameliorating reproductive failure in virus-infected mice. The findings support the notion that gestating dams require adequate amounts of dietary glutamine for the optimal survival and growth of embryos, fetuses, and neonates, and have important implications for nutritional support of mammals (including swine and humans) during gestation and lactation.


Porcine circovirus type 2 Pigs Nutrition Amino acids Reproductive failure 



C-Reactive protein






Porcine circovirus type 2


Quantitative polymerase chain reaction


Tumor necrosis factor-α



This research was jointly supported by National Natural Science Foundation of China (No. 31110103909, 30901041, 30972167, 30901040, 30928018, 30972156, 30871801, 30828024, 30828025, 30771558 and 30700581), National Basic Research Project (No. 2009CB118800), the CAS/SAFEA International Partnership Program for Creative Research Teams, the Thousand-People-Talent program at China Agricultural University, Ministry of Science and Technology of People’s Republic of China (No. (2010GB2D200322), Hunan Provincial Natural Science Foundation of China (No. 10JJ2028), and Texas AgriLife Research (No. 8200).

Conflict of interest

The authors declare no conflicts of interest.


  1. Allan GM, McNeilly F, Kennedy S et al (1998) Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe. J Vet Diagn Invest 10:3–10PubMedCrossRefGoogle Scholar
  2. Blachier F, Davila AM, Benamouzig R et al (2011) Channelling of arginine in NO and polyamine pathways in colonocytes and consequences. Front Biosci 16:1331–1343CrossRefGoogle Scholar
  3. Bonetto A, Penna F, Minero VG et al (2011) Glutamine prevents myostatin hyperexpression and protein hypercatabolism induced in C2C12 myotubes by tumor necrosis factor-α. Amino Acids 40:585–594PubMedCrossRefGoogle Scholar
  4. Castell L, Vance C, Abbott R et al (2004) Granule localization of glutaminase in human neutrophils and the consequence of glutamine utilization for neutrophil activity. J Biol Chem 279:13305–13310PubMedCrossRefGoogle Scholar
  5. Chen PF, Xu XG, Liu XS et al (2005) Characterisation of monoclonal antibodies to the TNF and TNF receptor families. Cell Immunol 236:78–85CrossRefGoogle Scholar
  6. Cooksey RC, McClain DA (2011) Increased hexosamine pathway flux and high fat feeding are not additive in inducing insulin resistance: evidence for a shared pathway. Amino Acids 40:841–846PubMedCrossRefGoogle Scholar
  7. Dai ZL, Li XL, Xi PB et al (2011) Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids. doi: 10.1007/s00726-011-0846-x
  8. Dinarello CA (1997) Interleukin-1. Cytokine Growth Factor Rev 8:253–265PubMedCrossRefGoogle Scholar
  9. Eamens GJ, Forbes WA, Djordjevic SP (2006) Characterisation of Erysipelothrix rhusiopathiae isolates from pigs associated with vaccine breakdowns. Vet Microbiol 115:329–338PubMedCrossRefGoogle Scholar
  10. Fang YZ, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879PubMedCrossRefGoogle Scholar
  11. Fenaux M, Halbur PG, Haqshenas G et al (2002) Cloned genomic DNA of type 2 porcine circovirus is infectious when injected directly into the liver and lymph nodes of pigs: characterization of clinical disease, virus distribution, and pathologic lesions. J Virol 76:541–551PubMedCrossRefGoogle Scholar
  12. Flynn NE, Wu G (1996) An important role for endogenous synthesis of arginine in maintaining arginine homeostasis in neonatal pigs. Am J Physiol Regul Integr Comp Physiol 271:R1149–R1155Google Scholar
  13. Fu WJ, Stromberg AJ, Viele K et al (2010) Statistics and bioinformatics in nutritional sciences: analysis of complex data in the era of systems biology. J Nutr Biochem 21:561–572PubMedCrossRefGoogle Scholar
  14. Grau-Roma L, Segales J (2007) Detection of porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, swine influenza virus and Aujeszky’s disease virus in cases of porcine proliferative and necrotizing pneumonia (PNP) in Spain. Vet Microbiol 119:144–151PubMedCrossRefGoogle Scholar
  15. Grau-Roma L, Fraile L, Segales J (2011) Recent advances in the epidemiology, diagnosis and control of diseases caused by porcine circovirus type 2. Vet J 187:23–32PubMedCrossRefGoogle Scholar
  16. Haynes TE, Li P, Li XL et al (2009) l-Glutamine or l-alanyl-l-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes. Amino Acids 37:131–142PubMedCrossRefGoogle Scholar
  17. Hou YQ, Wang L, Ding BY et al (2010) Dietary α-ketoglutarate supplementation ameliorates intestinal injury in lipopolysaccharide-challenged piglets. Amino Acids 39:555–564PubMedCrossRefGoogle Scholar
  18. Hou YQ, Wang L, Ding BY et al (2011) Alpha-ketoglutarate and intestinal function. Front Biosci 16:1186–1196CrossRefGoogle Scholar
  19. Huang RL, Yin YL, Wu GY et al (2005) Effect of dietary oligochitosan supplementation on ileal digestibility of nutrients and performance in broilers. Poul Sci 84:1383–1388Google Scholar
  20. Inoue Y, Grant JP, Snyder PJ (1993) Effect of glutamine-supplemented intravenous nutrition on survival after Escherichia coli-induced peritonitis. J Parenter Enteral Nutr 17:41–46CrossRefGoogle Scholar
  21. Jung BG, Toan NT, Cho SJ et al (2010) Dietary aluminosilicate supplement enhances immune activity in mice and reinforces clearance of porcine circovirus type 2 in experimentally infected pigs. Vet Microbiol 143:117–125PubMedCrossRefGoogle Scholar
  22. Kim J, Chung HK, Chae C (2003) Association of porcine circovirus 2 with porcine respiratory disease complex. Vet J 166:251–256PubMedCrossRefGoogle Scholar
  23. Kim J, Ha Y, Jung K et al (2004) Enteritis associated with porcine circovirus 2 in pigs. Can J Vet Res 68:218–221PubMedGoogle Scholar
  24. Kong XF, Zhang YZ, Yin YL et al (2009) Chinese Yam polysaccharide enhances growth performance and cellular immune response in weanling rats. J Sci Food Agric 89:2039–2044CrossRefGoogle Scholar
  25. Ladekjaer-Mikkelsen AS, Nielsen J, Storgaard T et al (2001) Transplacental infection with PCV-2 associated with reproductive failure in a gilt. Vet Rec 148:759–760PubMedGoogle Scholar
  26. Li P, Yin YL, Li D et al (2007) Amino acids and immune function. Br J Nutr 98:237–252PubMedCrossRefGoogle Scholar
  27. Li XL, Bazer FW, Johnson GA et al (2010) Dietary supplementation with 0.8% l-arginine between days 0 and 25 of gestation reduces litter size in gilts. J Nutr 140:1111–1116PubMedCrossRefGoogle Scholar
  28. Li XL, Rezaei R, Li P et al (2011) Composition of amino acids in feed ingredients for animal diets. Amino Acids 40:1159–1168PubMedCrossRefGoogle Scholar
  29. March CJ, MosleyB LarsenA et al (1985) Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315:641–647PubMedCrossRefGoogle Scholar
  30. Monroe S, Polk R (2000) Antimicrobial use and bacterial resistance. Curr Opin Microbiol 3:496–501PubMedCrossRefGoogle Scholar
  31. Mühling J, Tussing F, Nickolaus KA et al (2010) Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production. Amino Acids 38:167–177PubMedCrossRefGoogle Scholar
  32. Naugler WE, Karin M (2008) The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med 14:109–119PubMedCrossRefGoogle Scholar
  33. Opriessnig T, Thacker EL, Yu S et al (2004) Experimental reproduction of postweaning multisystemic wasting syndrome in pigs by dual infection with Mycoplasma hyopneumoniae and porcine circovirus type 2. Vet Pathol 41:624–640PubMedCrossRefGoogle Scholar
  34. Opriessnig T, Patterson AR, Meng XJ et al (2009) Porcine circovirus type 2 in muscle and bone marrow is infectious and transmissible to naive pigs by oral consumption. Vet Microbiol 133:54–64PubMedCrossRefGoogle Scholar
  35. Park JS, Kim J, Ha Y et al (2005) Birth abnormalities in pregnant sows infected intranasally with porcine circovirus 2. J Comp Pathol 132:139–144PubMedCrossRefGoogle Scholar
  36. Ren W, Yin YL, Liu G et al (2011) Effect of dietary arginine supplementation on reproductive performance of mice with porcine circovirus type 2 infection. Amino Acids. doi: 10.1007/s00726-011-0942-y
  37. Rogero MM, Borelli P, Fock RA et al (2010) Effects of glutamine on the nuclear factor-kappaB signaling pathway of murine peritoneal macrophages. Amino Acids 39:435–441PubMedCrossRefGoogle Scholar
  38. Rosell C, Segales J, Ramos-Vara JA et al (2000) Identification of porcine circovirus in tissues of pigs with porcine dermatitis and nephropathy syndrome. Vet Rec 146:40–43PubMedCrossRefGoogle Scholar
  39. Shewchuk LD, Baracos VE, Field CJ (1997) Dietary l-glutamine supplementation reduces the growth of the Morris Hepatoma 7777 in exercise-trained and sedentary rats. J Nutr 127:158–166PubMedGoogle Scholar
  40. Shi KC, Guo X, Ge XN et al (2010) Cytokine mRNA expression profiles in peripheral blood mononuclear cells from piglets experimentally co-infected with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2. Vet Microbiol 140:155–160PubMedCrossRefGoogle Scholar
  41. Sipos W, Duvigneau JC, Pietschmann P et al (2005) Porcine dermatitis and nephropathy syndrome (PDNS) is associated with a systemic cytokine expression profile indicative of proinflammation and a Th1 bias. Vet Immunol Immunopathol 107:303–313PubMedCrossRefGoogle Scholar
  42. Stevenson GW, Kiupel M, Mittal SK et al (2001) Tissue distribution and genetic typing of porcine circoviruses in pigs with naturally occurring congenital tremors. J Vet Diagn Invest 13:57–62PubMedCrossRefGoogle Scholar
  43. Suzuki I, Matsumoto Y, Adjei AA et al (1993) Effect of a glutamine-supplemented diet on response to methicillin-resistant Staphylococcus aureus infection in mice. J Nutr Sci Vitaminol (Tokyo) 39:405–410CrossRefGoogle Scholar
  44. Szalai AJ, Van Cott JL, McGhee JR et al (2000) Human C-reactive protein is protective against fatal Salmonella enterica serovar typhimurium infection in transgenic mice. Infect Immun 68:5652–5656PubMedCrossRefGoogle Scholar
  45. Tan BE, Yin YL, Kong XF et al (2010) l-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells. Amino Acids 38:1227–1235PubMedCrossRefGoogle Scholar
  46. Vincent AL, Ciacci-Zanella JR, Lorusso A et al (2010) Efficacy of inactivated swine influenza virus vaccines against the 2009 A/H1N1 influenza virus in pigs. Vaccine 28:2782–2787PubMedCrossRefGoogle Scholar
  47. Wallace C, Keast D (1992) Glutamine and macrophage function. Metabolism 41:1016–1020PubMedCrossRefGoogle Scholar
  48. Wei JW, Carroll RJ, Harden KK et al (2011) Comparisons of treatment means when factors do not interact in two-factorial studies. Amino Acids. doi: 10.1007/s00726-011-0924-0
  49. Wells SM, Kew S, Yaqoob P et al (1999) Dietary glutamine enhances cytokine production by murine macrophages. Nutrition 15:881–884PubMedCrossRefGoogle Scholar
  50. Wen L, He K, Yang H et al (2008) Complete nucleotide sequence of a novel porcine circovirus-like agent and its infectivity in vitro. Science in China C Life Sci 51:453–458CrossRefGoogle Scholar
  51. West KH, Bystrom JM, Wojnarowicz C et al (1999) Myocarditis and abortion associated with intrauterine infection of sows with porcine circovirus 2. J Vet Diagn Invest 11:530–532PubMedCrossRefGoogle Scholar
  52. Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17PubMedCrossRefGoogle Scholar
  53. Wu G (2010) Functional amino acids in growth, reproduction and health. Adv Nutr 1:31–37PubMedCrossRefGoogle Scholar
  54. Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17PubMedGoogle Scholar
  55. Wu G, Field CJ, Marliss EB (1991) Glutamine and glucose metabolism in rat splenocytes and mesenteric lymph node lymphocytes. Am J Physiol Endocrinol Metab 260:E141–E147Google Scholar
  56. Wu G, Knabe DA, Flynn NE et al (1996) Arginine degradation in developing porcine enterocytes. Am J Physiol Gastrointest Liver Physiol 271:G913–G919Google Scholar
  57. Wu G, Fang YZ, Yang S et al (2004) Glutathione metabolism and its implications for health. J Nutr 134:489–492PubMedGoogle Scholar
  58. Wu G, Bazer FW, Wallace JM et al (2006) Intrauterine growth retardation: Implications for the animal sciences. J Anim Sci 84:2316–2337PubMedCrossRefGoogle Scholar
  59. Wu G, Bazer FW, Burghardt RC et al (2010a) Impacts of amino acid nutrition on pregnancy outcome in pigs: mechanisms and implications for swine production. J Anim Sci 88:E195–E204PubMedCrossRefGoogle Scholar
  60. Wu X, Ruan Z, Gao YL et al (2010b) Dietary supplementation with l-arginine or N-carbamylglutamate enhances intestinal growth and heat shock protein-70 expression in weanling pigs fed a corn- and soybean meal-based diet. Amino Acids 39:831–839PubMedCrossRefGoogle Scholar
  61. Wu G, Bazer FW, Johnson GA et al (2011a) Important roles for l-glutamine in swine nutrition and production. J Anim Sci 89:2017–2030PubMedCrossRefGoogle Scholar
  62. Wu G, Bazer FW, Burghardt RC et al (2011b) Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids 40:1053–1063PubMedCrossRefGoogle Scholar
  63. Xi PB, Jiang ZY, Zheng CT et al (2011) Regulation of protein metabolism by glutamine: implications for nutrition and health. Front Biosci 16:578–597CrossRefGoogle Scholar
  64. Yao K, Yin YL, Li XL et al (2011) Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells. Amino Acids. doi: 10.1007/s00726-011-1060-6
  65. Yin YL, Zhong HY, Huang RL et al (1993) Nutritive value of feedstuffs and diets for pigs. I. Chemical composition, apparent ileal and fecal digestibility. Anim Feed Sci Tech 44:1–27CrossRefGoogle Scholar
  66. Yin YL, Li TJ, Huang RL (2008a) Evaluating standardized ileal digestibility of amino acids in growing pigs. Anim Feed Sci Tech 140:385–401CrossRefGoogle Scholar
  67. Yin YL, Tang ZR, Sun ZH et al (2008b) Effect of galacto-mannan-oligosaccharides or chitosan supplementation on cytoimmunity and humoral immunity response in early-weaned piglets. Asian-Aust J Anim Sci 21:723–731Google Scholar
  68. Yin FG, Zhang ZZ, Huang J et al (2010a) Digestion rate of dietary starch affects systemic circulation of amino acids in weaned pigs. Br J Nutr 103:1404–1412PubMedCrossRefGoogle Scholar
  69. Yoo SS, Field CJ, McBurney MI (1997) Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs. J Nutr 127:2253–2259PubMedGoogle Scholar
  70. Yoon KJ, Jepsen RJ, Pogranichniy RM et al (2004) A novel approach to intrauterine viral inoculation of swine using PCV type 2 as a model. Theriogenology 61:1025–1037PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Wenkai Ren
    • 1
    • 3
  • Wei Luo
    • 2
  • Miaomiao Wu
    • 1
  • Gang Liu
    • 1
  • Xinglong Yu
    • 2
  • Jun Fang
    • 3
  • Teijun Li
    • 1
  • Yulong Yin
    • 1
  • Guoyao Wu
    • 1
    • 4
    • 5
  1. 1.Research Center for Healthy Breeding of Livestock and Poultry, Key Laboratory for Agro-ecological Processes in Subtropical RegionHunan Engineering and Research Center of Animal and Poultry Science, Institute of Subtropical Agriculture, The Chinese Academy of SciencesChangshaChina
  2. 2.College of Veterinary MedicineHunan Agricultural UniversityChangshaChina
  3. 3.College of Bioscience and BiotechnologyHunan Agricultural UniversityChangshaChina
  4. 4.State Key Laboratory of Animal NutritionChina Agricultural UniversityBeijingChina
  5. 5.Department of Animal ScienceTexas A & M UniversityCollege StationUSA

Personalised recommendations