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Impacts of arginine nutrition on embryonic and fetal development in mammals

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Abstract

Embryonic loss and intrauterine growth restriction (IUGR) are significant problems in humans and other animals. Results from studies involving pigs and sheep have indicated that limited uterine capacity and placental insufficiency are major factors contributing to suboptimal reproduction in mammals. Our discovery of the unusual abundance of the arginine family of amino acids in porcine and ovine allantoic fluids during early gestation led to the novel hypothesis that arginine plays an important role in conceptus (embryo and extra-embryonic membranes) development. Arginine is metabolized to ornithine, proline, and nitric oxide, with each having important physiological functions. Nitric oxide is a vasodilator and angiogenic factor, whereas ornithine and proline are substrates for uterine and placental synthesis of polyamines that are key regulators of gene expression, protein synthesis, and angiogenesis. Additionally, arginine activates the mechanistic (mammalian) target of rapamycin cell signaling pathway to stimulate protein synthesis in the placenta, uterus, and fetus. Thus, dietary supplementation with 0.83 % l-arginine to gilts consuming 2 kg of a typical gestation diet between either days 14 and 28 or between days 30 and 114 of pregnancy increases the number of live-born piglets and litter birth weight. Similar results have been reported for gestating rats and ewes. In sheep, arginine also stimulates development of fetal brown adipose tissue. Furthermore, oral administration of arginine to women with IUGR has been reported to enhance fetal growth. Collectively, enhancement of uterine as well as placental growth and function through dietary arginine supplementation provides an effective solution to improving embryonic and fetal survival and growth.

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Abbreviations

ADC:

Arginine decarboxylase

AGAT:

Arginine:glycine amidinotransferase

CAT:

Cationic amino acid transporter

α-DFMO:

dl-α-Difluoromethylornithine

GE:

Glandular epithelium

IUGR:

Intrauterine growth restriction

LE:

Luminal epithelium

MTOR:

Mammalian target of rapamycin

NO:

Nitric oxide

NOS:

NO synthase

ODC:

Ornithine decarboxylase

P5C:

Pyrroline-5-carboxylate

SAM:

S-adenosylmethionine

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Acknowledgments

Work in our laboratories was supported by National Research Initiative Competitive Grants from the Animal Reproduction Program (2008-35203-19120, 2009-35206-05211 and 2011-67015-20028) and Animal Growth & Nutrient Utilization Program (2008-35206-18764) of the USDA National Institute of Food and Agriculture, AHA (10GRNT4480020), Texas A&M AgriLife Research (H-8200), the National Natural Science Foundation of China (u0731001, 30810103902, 31172217, 31272449, and 31272450), China Postdoctoral Science Foundation (2012T50163), Chinese Universities Scientific Funds (2012RC024), and the Thousand-People Talent program at China Agricultural University. Important contributions of our graduate students and colleagues to the recent development of this field of research are gratefully appreciated.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Animal Science, Texas A&M University, College Station, 77843, USA

    Guoyao Wu, Fuller W. Bazer, M. Carey Satterfield, Xilong Li & Xiaoqiu Wang

  2. Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, 77843, USA

    Gregory A. Johnson & Robert C. Burghardt

  3. State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China

    Guoyao Wu, Zhaolai Dai, Junjun Wang & Zhenlong Wu

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  1. Guoyao Wu
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  2. Fuller W. Bazer
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Wu, G., Bazer, F.W., Satterfield, M.C. et al. Impacts of arginine nutrition on embryonic and fetal development in mammals. Amino Acids 45, 241–256 (2013). https://doi.org/10.1007/s00726-013-1515-z

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