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RESEARCH ARTICLE

Dietary rumen-protected arginine and N-carbamylglutamate supplementation enhances fetal growth in underfed ewes

Lingwei Sun A B C , Hao Zhang A , Ziyu Wang A , Yixuan Fan A , Yixuan Guo A and Feng Wang A D
+ Author Affiliations
- Author Affiliations

A Jiangsu Engineering Technology Research Center of Meat Sheep and Goat Industry, Nanjing Agricultural University, #1, Tongwei Road, Nanjing, Jiangsu Province, 210095, PR China.

B Institute of Animal Science and Veterinary Medicine, Shanghai Academy of Agricultural Sciences, #2901, Beidi Road, Shanghai, 201106, PR China.

C Division of Animal Genetic Engineering, Shanghai Municipal Key Laboratory of Agri-genetics and Breeding, #2901, Beidi Road, Shanghai, 201106, PR China.

D Corresponding author. Email: caeet@njau.edu.cn

Reproduction, Fertility and Development 30(8) 1116-1127 https://doi.org/10.1071/RD17164
Submitted: 28 April 2017  Accepted: 29 December 2017   Published: 8 February 2018

Abstract

The present study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary rumen-protected l-arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation in underfed ewes is effective in enhancing fetal growth. Between Days 35 and 110 of pregnancy, 32 multiparous ewes carrying two fetuses were randomly assigned to one of four groups: a control (CG) group (n = 8; 100% National Research Council (NRC) requirements for pregnant sheep), a nutrient-restricted (RG) group (n = 8; fed 50% NRC requirements, and two treatment (ARG and NCG) groups (n = 8 in each group; fed 50% NRC requirements supplemented with 20 g day−1 RP-Arg or 5 g day−1 NCG. All ewes were killed on Day 110 of pregnancy to determine fetal weight and fetal organ weights, and metabolites and hormones in fetal plasma, amino acid concentrations in the fetal liver and longissimus dorsi muscle, and expression of mRNAs in the somatotropic axis. Maternal and fetal bodyweight and the weight of most fetal organs expressed as a percentage of bodyweight increased in response to ARG and NCG compared with values for fetuses from RG ewes. Fetal plasma concentrations of insulin, insulin-like growth factor 1, total amino acids, lactate, thyroxine, and the thyroxine/tri-iodothyronine ratio were lower in fetuses from RG ewes compared with the other treatment groups, but concentrations of growth hormone, non-esterified fatty acids, and total cholesterol were greater in fetuses from RG ewes. Maternal RP-Arg or NCG supplementation increased concentrations of amino acids in fetal tissues and expression of mRNAs for somatotropic axis proteins in fetuses from RG ewes. These findings suggest that maternal RP-Arg and NCG supplementation of underfed ewes decreases fetal IUGR by improving metabolic homeostasis of fetal endocrinology, increasing the availability of amino acids in the fetal liver and longissimus dorsi muscle and affecting the expression of somatotropic axis genes.

Additional keywords: amino acids, arginine, fetus, Hu sheep, somatotropic axis, undernutrition.


References

Barker, D. J. (1997). The long-term outcome of retarded fetal growth. Clin. Obstet. Gynecol. 40, 853–863.
| 1:STN:280:DyaK1c%2FptFKgtg%3D%3D&md5=bcf10a2598f974ca403d1ef3ae0866d8CAS |

Belkacemi, L., Jelks, A., Chen, C. H., Ross, M. G., and Desai, M. (2011). Altered placental development in undernourished rats: role of maternal glucocorticoids. Reprod. Biol. Endocrinol. 9, 105.
Altered placental development in undernourished rats: role of maternal glucocorticoids.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFGktr3O&md5=e1ab43124536aa620ee7d932caac210bCAS |

Benhalima, K., Leuridan, L., Calewaert, P., Devlieger, R., Verhaeghe, J., and Mathieu, C. (2014). Glucose intolerance after a recent history of gestational diabetes. Int. J. Endocrinol. 2014, 727652.
Glucose intolerance after a recent history of gestational diabetes.Crossref | GoogleScholarGoogle Scholar |

Blachier, F., Davila, A. M., Benamouzig, R., and Tome, D. (2011). Channelling of arginine in NO and polyamine pathways in colonocytes and consequences. Front. Biosci. (Landmark Ed.) 16, 1331–1343.
Channelling of arginine in NO and polyamine pathways in colonocytes and consequences.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXisVylsL0%3D&md5=97de26fdd84f70056f898ec6138c1088CAS |

Blasco-Alonso, J., Rosa, C. V., Camacho Alonso, J. M., and Milano, M. G. (2015). [Citrulline and arginine kinetics and its value as a prognostic factor in pediatric critically ill patients.] An. Pediatr. (Barc.) 83, 257–263.
| 1:STN:280:DC%2BC2MrntlWrtQ%3D%3D&md5=15739a3f2882176adedf5d01139226b4CAS |

Brown, L. D., Rozance, P. J., Bruce, J. L., Friedman, J. E., Hay, W., and Wesolowski, S. R. (2015). Limited capacity for glucose oxidation in fetal sheep with intrauterine growth restriction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 309, R920–R928.
Limited capacity for glucose oxidation in fetal sheep with intrauterine growth restriction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XmtlGrtbs%3D&md5=d6a61eb6df43a790db9ca6ddc630a2adCAS |

Cao, W., Xiao, L., Liu, G., Fang, T., Wu, X., Jia, G., Zhao, H., Chen, X., Wu, C., and Cai, J. (2016). Dietary arginine and N-carbamylglutamate supplementation enhances the antioxidant statuses of the liver and plasma against oxidative stress in rats. Food Funct. 7, 2303–2311.
Dietary arginine and N-carbamylglutamate supplementation enhances the antioxidant statuses of the liver and plasma against oxidative stress in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XmsF2mtrY%3D&md5=395766662087f3977948c75f86cc3191CAS |

Carless, M. A., Curran, J. E., Gaffney, P., Weinstein, S. R., and Griffiths, L. R. (2001). Association analysis of somatostatin receptor (SSTR1 and SSTR2) polymorphisms in breast cancer and solar keratosis. Cancer Lett. 166, 193–197.
Association analysis of somatostatin receptor (SSTR1 and SSTR2) polymorphisms in breast cancer and solar keratosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXislGku7Y%3D&md5=473f81ccf2979aa885b3d6730053230aCAS |

Cetin, I., Ronzoni, S., Marconi, A. M., Perugino, G., Corbetta, C., Battaglia, F. C., and Pardi, G. (1996). Maternal concentrations and fetal–maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies. Am. J. Obstet. Gynecol. 174, 1575–1583.
Maternal concentrations and fetal–maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK283ktVSqtg%3D%3D&md5=a97071b13360d36e9e824d6a457e6350CAS |

Chacher, B., Wang, D. M., Liu, H. Y., and Liu, J. X. (2012). Degradation of l-arginine and N-carbamoyl glutamate and their effect on rumen fermentation in vitro. Ital. J. Anim. Sci. 11, 4693–4696.
Degradation of l-arginine and N-carbamoyl glutamate and their effect on rumen fermentation in vitro.Crossref | GoogleScholarGoogle Scholar |

Chacher, B., Liu, H., Wang, D., and Liu, J. (2013). Potential role of N-carbamoyl glutamate in biosynthesis of arginine and its significance in production of ruminant animals. J. Anim. Sci. Biotechnol. 4, 16.
Potential role of N-carbamoyl glutamate in biosynthesis of arginine and its significance in production of ruminant animals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXns1Orsr0%3D&md5=3bcb1fe47b85541b9a1ff72928da5973CAS |

Clot, J. P., Crosnier, H., Guest, G., Saucet, C., Souberbielle, J. C., Andre, J. L., Broyer, M., Rappaport, R., and Benelli, C. (2001). Effects of growth hormone on growth factors after renal transplantation. Pediatr. Nephrol. 16, 397–403.
Effects of growth hormone on growth factors after renal transplantation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3Mzkt1artQ%3D%3D&md5=555a11942aeede575b1a51da80ec5fafCAS |

Davis, T. A., Fiorotto, M. L., Burrin, D. G., Reeds, P. J., Nguyen, H. V., Beckett, P. R., Vann, R. C., and O’Connor, P. M. (2002). Stimulation of protein synthesis by both insulin and amino acids is unique to skeletal muscle in neonatal pigs. Am. J. Physiol. Endocrinol. Metab. 282, E880–E890.
Stimulation of protein synthesis by both insulin and amino acids is unique to skeletal muscle in neonatal pigs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XivVels74%3D&md5=07d4f55339036691a4bc9a3e73dd88b5CAS |

Dumortier, O., Blondeau, B., Duvillié, B., Reusens, B., Bréant, B., and Remacle, C. (2007). Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet. Diabetologia 50, 2495–2503.
Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1Kku7jF&md5=31001b7fd79a8760dd67b774359969f6CAS |

Ekloulawson, M., Bernard, F., Neveux, N., Chaumontet, C., Bos, C., Davilagay, A. M., Tomé, D., Cynober, L., and Blachier, F. (2009). Colonic luminal ammonia and portal blood l-glutamine and l-arginine concentrations: a possible link between colon mucosa and liver ureagenesis. Amino Acids 37, 751–760.
Colonic luminal ammonia and portal blood l-glutamine and l-arginine concentrations: a possible link between colon mucosa and liver ureagenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFyqt7jF&md5=b425b040ff50ddc1cf91be6077cbed51CAS |

Eremia, S. C., Boo, H. A. D., Bloomfield, F. H., Oliver, M. H., Harding, J. E., Jane, P., and Harding, E. (2007). Fetal and amniotic insulin-like growth factor (IGF-1) supplements improve growth rate in IUGR fetal sheep. Endocrinology 148, 2963–2972.
Fetal and amniotic insulin-like growth factor (IGF-1) supplements improve growth rate in IUGR fetal sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmt1ajurg%3D&md5=ff8ebfc974f6ff084f6e5197e6362ff2CAS |

Ford, S. P., Hess, B. W., Schwope, M. M., Nijland, M. J., Gilbert, J. S., Vonnahme, K. A., Means, W. J., Han, H., and Nathanielsz, P. W. (2007). Maternal undernutrition during early to mid-gestation in the ewe results in altered growth, adiposity, and glucose tolerance in male offspring. J. Anim. Sci. 85, 1285–1294.
Maternal undernutrition during early to mid-gestation in the ewe results in altered growth, adiposity, and glucose tolerance in male offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksF2hur8%3D&md5=5ba4b8e9a57bbbab5b433b545e68bfb2CAS |

Fowden, A. L. (1993). Insulin deficiency: effects on fetal growth and development. J. Paediatr. Child Health 29, 6–11.
Insulin deficiency: effects on fetal growth and development.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3s3htlGrtw%3D%3D&md5=6400054d929415f52a45e343928d28c9CAS |

Fowden, A. L. (1995). Endocrine regulation of fetal growth. Reprod. Fertil. Dev. 7, 351–363.
Endocrine regulation of fetal growth.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXpvVShtr4%3D&md5=4d969121706248a3b9d2a5d9460b7007CAS |

Furness, D. L., Fenech, M. F., Khong, Y. T., Romero, R., and Dekker, G. A. (2008). One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency. Am. J. Obstet. Gynecol. 199, 276.e1–276.e8.
One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency.Crossref | GoogleScholarGoogle Scholar |

Gao, F., Liu, Y. C., and Hou, X. Z. (2013). Effect of maternal undernutrition during late pregnancy on hormonal status and metabolic changes in neonatal lambs. Czech J. Anim. Sci. 58, 15–20.
| 1:CAS:528:DC%2BC3sXitFGqu7g%3D&md5=c516d5f12d7443dddd306c6e577ea541CAS |

Gao, F., Liu, Y., Li, L., Li, M., Zhang, C., Ao, C., and Hou, X. (2014). Effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver. Anim. Reprod. Sci. 147, 99–105.
Effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXosFamsrg%3D&md5=edda37973866f32219056ca77fe0279fCAS |

Gluckman, P. D., and Hanson, M. A. (2006). The consequences of being born small – an adaptive perspective. Horm. Res. 65, 5–14.
| 1:CAS:528:DC%2BD28XksV2isLk%3D&md5=6c6e929cbe59625bf8b23caa5bf7e72dCAS |

Henry, B. A., Rao, A., Tilbrook, A. J., and Clarke, I. J. (2001). Chronic food-restriction alters the expression of somatostatin and growth hormone-releasing hormone in the ovariectomised ewe. J. Endocrinol. 170, R1–R5.
Chronic food-restriction alters the expression of somatostatin and growth hormone-releasing hormone in the ovariectomised ewe.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXltlaksLo%3D&md5=678f281d72a3dd16d3252da398849fdbCAS |

Horikawa, R., Tachibana, T., Katsumata, N., Ishikawa, H., and Tanaka, T. (2000). Regulation of pituitary growth hormone-secretagogue and growth hormone-releasing hormone receptor RNA expression in young Dwarf rats. Endocr. J. 47, S53–S56.
Regulation of pituitary growth hormone-secretagogue and growth hormone-releasing hormone receptor RNA expression in young Dwarf rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXktlGgs70%3D&md5=c50ccb9516aea9e0dd9ad4f7dd03f6baCAS |

Hyatt, M. A., Walker, D. A., Stephenson, T., and Symonds, M. E. (2004). Ontogeny and nutritional manipulation of the hepatic prolactin-growth hormone-insulin-like growth factor axis in the ovine fetus and in neonate and juvenile sheep. Proc. Nutr. Soc. 63, 127–135.
Ontogeny and nutritional manipulation of the hepatic prolactin-growth hormone-insulin-like growth factor axis in the ovine fetus and in neonate and juvenile sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXktFGlu70%3D&md5=c30e23594d7744998f5d775aa4e89363CAS |

Kim, S. H., and Park, M. J. (2017). Effects of growth hormone on glucose metabolism and insulin resistance in human. Ann. Pediatr. Endocrinol. Metab. 22, 145–152.
Effects of growth hormone on glucose metabolism and insulin resistance in human.Crossref | GoogleScholarGoogle Scholar |

Kim, J., Song, G., Wu, G., Gao, H., Johnson, G. A., and Bazer, F. W. (2014). Arginine, leucine, and glutamine stimulate proliferation of porcine trophectoderm cells through the mTOR–RPS6K–RPS6–EIF4EBP1 signal transduction pathway. Biol. Reprod. 88, 113.
Arginine, leucine, and glutamine stimulate proliferation of porcine trophectoderm cells through the mTOR–RPS6K–RPS6–EIF4EBP1 signal transduction pathway.Crossref | GoogleScholarGoogle Scholar |

Lassala, A., Bazer, F. W., Cudd, T. A., Li, P., Li, X., Satterfield, M. C., Spencer, T. E., and Wu, G. (2009). Intravenous administration of l-citrulline to pregnant ewes is more effective than l-arginine for increasing arginine availability in the fetus. J. Nutr. 139, 660–665.
Intravenous administration of l-citrulline to pregnant ewes is more effective than l-arginine for increasing arginine availability in the fetus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjslSkt7w%3D&md5=53f0dab50e5f14d649e48c6672adb8a6CAS |

Lassala, A., Bazer, F. W., Cudd, T. A., Datta, S., Keisler, D. H., Satterfield, M. C., Spencer, T. E., and Wu, G. (2011). Parenteral administration of l-arginine enhances fetal survival and growth in sheep carrying multiple fetuses. J. Nutr. 141, 849–855.
Parenteral administration of l-arginine enhances fetal survival and growth in sheep carrying multiple fetuses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXltlCqtbo%3D&md5=68527697bceb2939234c04093a27ca09CAS |

Lin, G., Wang, X., Wu, G., Feng, C., Zhou, H., Li, D., and Wang, J. (2014). Improving amino acid nutrition to prevent intrauterine growth restriction in mammals. Amino Acids 46, 1605–1623.
Improving amino acid nutrition to prevent intrauterine growth restriction in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXkslGltLw%3D&md5=d1f36594cf119ab623ec11bdb4530f4eCAS |

Lipsett, J., Tamblyn, M., Madigan, K., Roberts, P., Cool, J. C., Runciman, S. I., Mcmillen, I. C., Robinson, J., and Owens, J. A. (2006). Restricted fetal growth and lung development: a morphometric analysis of pulmonary structure. Pediatr. Pulmonol. 41, 1138–1145.
Restricted fetal growth and lung development: a morphometric analysis of pulmonary structure.Crossref | GoogleScholarGoogle Scholar |

Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) method. Methods 25, 402–408.
Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFelt7s%3D&md5=a80b5e0841c49e736a3564bfe77a7aa6CAS |

McCoard, S., Sales, F., Wards, N., Sciascia, Q., Oliver, M., Koolaard, J., and Linden, D. V. D. (2013). Parenteral administration of twin-bearing ewes with l-arginine enhances the birth weight and brown fat stores in sheep. Springerplus 2, 684.
Parenteral administration of twin-bearing ewes with l-arginine enhances the birth weight and brown fat stores in sheep.Crossref | GoogleScholarGoogle Scholar |

Neville, T. L., Ward, M. A., Reed, J. J., Sotonavarro, S. A., Julius, S. L., Borowicz, P. P., Taylor, J. B., Redmer, D. A., Reynolds, L. P., and Caton, J. S. (2008). Effects of level and source of dietary selenium on maternal and fetal body weight, visceral organ mass, cellularity estimates, and jejunal vascularity in pregnant ewe lambs. J. Anim. Sci. 86, 890–901.
Effects of level and source of dietary selenium on maternal and fetal body weight, visceral organ mass, cellularity estimates, and jejunal vascularity in pregnant ewe lambs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjvFeruro%3D&md5=629b785c15cd3d19ea3c87f05e39940eCAS |

Nie, H. T., Wang, Z. Y., Lan, S., Zhang, H., Wan, Y. J., Fan, Y. X., Zhang, Y. L., and Wang, F. (2015). Effect of residual feed intake phenotype–nutritional treatment interaction on the growth performance, plasma metabolic variables and somatotropic axis gene expression of growing ewes. Anim. Prod. Sci. 56, 1593–1604.
Effect of residual feed intake phenotype–nutritional treatment interaction on the growth performance, plasma metabolic variables and somatotropic axis gene expression of growing ewes.Crossref | GoogleScholarGoogle Scholar |

National Research Council (NRC) (1985). ‘Nutrient Requirements of Sheep (6th ed.).’ (National Academy Press: Washington, DC)

Pillai, S., Jones, A., Hoffman, M., Mcfadden, K., Reed, S., Zinn, S., and Govoni, K. (2017). Fetal and organ development at gestational days 45, 90, 135 and at birth of lambs exposed to under- or over-nutrition during gestation. Transl. Anim. Sci. 1, 16–25.
Fetal and organ development at gestational days 45, 90, 135 and at birth of lambs exposed to under- or over-nutrition during gestation.Crossref | GoogleScholarGoogle Scholar |

Rhind, S. M. (2004). Effects of maternal nutrition on fetal and neonatal reproductive development and function. Anim. Reprod. Sci. 82–83, 169–181.

Romero, C. J., Pinetwaddell, E., Sima, D. I., Miller, R. S., He, L., Wondisford, F., and Radovick, S. (2012). Insulin-like growth factor 1 mediates negative feedback to somatotroph GH expression via POU1F1/CREB binding protein interactions. Mol. Cell. Biol. 32, 4258–4269.
Insulin-like growth factor 1 mediates negative feedback to somatotroph GH expression via POU1F1/CREB binding protein interactions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhs1Siur%2FJ&md5=adb9d176baee0f0609fc0095986815dbCAS |

Russel, A. (1984). Body condition scoring of sheep. In Pract. 6, 91–93.
Body condition scoring of sheep.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c3jvVChsg%3D%3D&md5=686c345b77f01bfb405ae17dd3d188b2CAS |

Satterfield, M. C., Dunlap, K. A., Keisler, D. H., Bazer, F. W., and Wu, G. (2013). Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep. Amino Acids 45, 489–499.
Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXht1OitLrL&md5=0f449bf98e64448694a394bc0d983222CAS |

Sebert, S. P., Dellschaft, N. S., Chan, L. L. Y., Street, H., Henry, M., Francois, C., Sharma, V., Fainberg, H. P., Patel, N., and Roda, J. (2011). Maternal nutrient restriction during late gestation and early postnatal growth in sheep differentially reset the control of energy metabolism in the gastric mucosa. Endocrinology 152, 2816–2826.
Maternal nutrient restriction during late gestation and early postnatal growth in sheep differentially reset the control of energy metabolism in the gastric mucosa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXosFait70%3D&md5=020b0302e49b3dd4a2a7c2d8cb4e0938CAS |

Shields, B. M., Knight, B. A., Hill, A., Hattersley, A. T., and Vaidya, B. (2011). Fetal thyroid hormone level at birth is associated with fetal growth. J. Clin. Endocrinol. Metab. 96, E934–E938.
Fetal thyroid hormone level at birth is associated with fetal growth.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnt1Cht7c%3D&md5=309a6ec9d9500b8b77c3906aadb8b031CAS |

Strobl, J. S. (1994). Human growth hormone. Pharmacol. Rev. 46, 1–34.
| 1:CAS:528:DyaK2cXktVSqtL4%3D&md5=a02244277fca63fb11b10f50015dce8cCAS |

Sugihara, H., Emoto, N., Tamura, H., Kamegai, J., Shibasaki, T., Minami, S., and Wakabayashi, I. (1999). Effect of insulin-like growth factor-I on growth hormone-releasing factor receptor expression in primary rat anterior pituitary cell culture. Neurosci. Lett. 276, 87–90.
Effect of insulin-like growth factor-I on growth hormone-releasing factor receptor expression in primary rat anterior pituitary cell culture.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXntlemurs%3D&md5=85b749347d2c80d4de0b8736977161c8CAS |

Sun, L., Zhang, H., Fan, Y., Guo, Y., Zhang, G., Nie, H., and Wang, F. (2017). Metabolomic profiling in umbilical venous plasma reveals effects of dietary rumen-protected arginine or N-carbamylglutamate supplementation in nutrient-restricted Hu sheep during pregnancy. Reprod. Domest. Anim. 52, 376–388.
Metabolomic profiling in umbilical venous plasma reveals effects of dietary rumen-protected arginine or N-carbamylglutamate supplementation in nutrient-restricted Hu sheep during pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXntVOmu7w%3D&md5=c78d640a739c4be2ed7589cda33de962CAS |

Torre, I., González-Tendero, A., García-Cañadilla, P., Crispi, F., García-García, F., Bijnens, B., Iruretagoyena, I., Dopazo, J., Amat-Roldán, I., and Gratacós, E. (2014). Permanent cardiac sarcomere changes in a rabbit model of intrauterine growth restriction. PLoS One 9, e113067.
Permanent cardiac sarcomere changes in a rabbit model of intrauterine growth restriction.Crossref | GoogleScholarGoogle Scholar |

Treppiedi, D., Peverelli, E., Giardino, E., Ferrante, E., Calebiro, D., Spada, A., and Mantovani, G. (2017). Somatostatin receptor type 2 (SSTR2) internalization and intracellular trafficking in pituitary GH-secreting adenomas: role of scaffold proteins and implications for pharmacological resistance. Horm. Metab. Res. 49, 259–268.
Somatostatin receptor type 2 (SSTR2) internalization and intracellular trafficking in pituitary GH-secreting adenomas: role of scaffold proteins and implications for pharmacological resistance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhsFWltrjK&md5=dbccf3311a84e1bb99b0103f7a54c071CAS |

van Vliet, E., Eixarch, E., Illa, M., Arbat-Plana, A., González-Tendero, A., Hogberg, H. T., Zhao, L., Hartung, T., and Gratacos, E. (2013). Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain. PLoS One 8, e64545.
Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXptlyju70%3D&md5=c675d2fbb11b8a3087d630d09454ff4fCAS |

Wang, B., Qin, C., Zhang, C., Jia, J., Sun, C., and Li, W. (2014). Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides). Mol. Cell. Endocrinol. 382, 851–859.
Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXlt1Sktw%3D%3D&md5=b0ed468be8956360c424751255a38e13CAS |

Wu, G. Y., Gunasekara, A., Brunengraber, H., and Marliss, E. B. (1991). Effects of extracellular pH, CO2, and HCO3− on ketogenesis in perfused rat liver. Am. J. Physiol. 261, E221–E226.
| 1:STN:280:DyaK3Mzjs1eqtA%3D%3D&md5=c1f89c9d88f6bb8fcebbd66a408135caCAS |

Wu, G., Bazer, F. W., Cudd, T. A., Meininger, C. J., and Spencer, T. E. (2004). Maternal nutrition and fetal development. J. Nutr. 134, 2169–2172.
| 1:CAS:528:DC%2BD2cXns1ejtLg%3D&md5=4db8cbd0d7a1102cb2331e40b6542584CAS |

Xie, L., Antonowschlorke, I., Schwab, M., Mcdonald, T. J., Nathanielsz, P. W., and Li, C. (2013). The frontal cortex IGF system is down regulated in the term, intrauterine growth restricted fetal baboon. Growth Horm. IGF Res. 23, 187–192.
The frontal cortex IGF system is down regulated in the term, intrauterine growth restricted fetal baboon.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXht1emt7vJ&md5=cc766f1294d5b2cc8a3c7ebccd8d5e7aCAS |

Yang, H., Fu, D., Shao, H., Kong, X., Wang, W., Yang, X., Nyachoti, C. M., and Yin, Y. (2012). Impacts of birth weight on plasma, liver and skeletal muscle neutral amino acid profiles and intestinal amino acid transporters in suckling Huanjiang mini-piglets. PLoS One 7, e50921.
Impacts of birth weight on plasma, liver and skeletal muscle neutral amino acid profiles and intestinal amino acid transporters in suckling Huanjiang mini-piglets.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvV2qsbzP&md5=ef66a6cf34e9fbf380c5759a37d09b2dCAS |

Yin, F., Zhang, Z., Huang, J., and Yin, Y. (2010). Digestion rate of dietary starch affects systemic circulation of amino acids in weaned pigs. Br. J. Nutr. 103, 1404–1412.
Digestion rate of dietary starch affects systemic circulation of amino acids in weaned pigs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmtFWqsL4%3D&md5=142d8359fc4a8f851e5ed451af283d4aCAS |

Zhang, H., Sun, L. W., Wang, Z. Y., Deng, M. T., Zhang, G. M., Guo, R. H., Ma, T. W., and Wang, F. (2016a). Dietary N-carbamylglutamate and rumen-protected-arginine supplementation ameliorate fetal growth restriction in undernourished ewes. J. Anim. Sci. 94, 2072–2085.
Dietary N-carbamylglutamate and rumen-protected-arginine supplementation ameliorate fetal growth restriction in undernourished ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhsVCksL%2FM&md5=3f7709371c03bc455428253149d42931CAS |

Zhang, H., Sun, L. W., Wang, Z. Y., Deng, M. T., Nie, H. T., Zhang, G. M., Ma, T. W., and Wang, F. (2016b). N-Carbamylglutamate and l-arginine improves maternal and placental function in underfed ewes. Reproduction 151, 623–635.
N-Carbamylglutamate and l-arginine improves maternal and placental function in underfed ewes.Crossref | GoogleScholarGoogle Scholar |

Zheng, C. A., Huang, C. F., Cao, Y. H., Wang, J. J., and Bing, D. (2009). Branched-chain amino acids reverse the growth of intrauterine growth retardation rats in a malnutrition model. Asian-Australas. J. Anim. Sci. 22, 1495–1503.
Branched-chain amino acids reverse the growth of intrauterine growth retardation rats in a malnutrition model.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXotVGmtA%3D%3D&md5=9c8013622730d2da8e450541d1ff6c58CAS |