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Dietary supplementation with l-arginine between days 14 and 25 of gestation enhances NO and polyamine syntheses and the expression of angiogenic proteins in porcine placentae

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Abstract

Dietary supplementation with 0.4 or 0.8% l-arginine (Arg) to gilts between days 14 and 25 of gestation enhances embryonic survival and vascular development in placentae; however, the underlying mechanisms are largely unknown. This study tested the hypothesis that Arg supplementation stimulated placental expression of mRNAs and proteins that enhance angiogenesis, including endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), placental growth factor (PGF), GTP cyclohydrolase-I (GTP-CH1), ornithine decarboxylase (ODC1), and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2). Beginning on the day of breeding, gilts were fed daily 2 kg of a corn–soybean meal-based diet supplemented with 0.0 (control), 0.4, or 0.8% Arg. On day 25 of gestation, gilts were hysterectomized to obtain uteri and conceptuses for histochemical and biochemical analyses. eNOS and VEGFR1 proteins were localized to endothelial cells of maternal uterine blood vessels and to the uterine luminal epithelium, respectively. Compared with the control, dietary supplementation with 0.4 or 0.8% Arg increased (P < 0.05) the amounts of nitrite plus nitrate (NOx; oxidation products of NO) and polyamines in allantoic and amniotic fluids, concentrations of NOx, tetrahydrobiopterin (BH4, an essential cofactor for all NOS isoforms) and polyamines in placentae, as well as placental protein abundances of GTP-CH1 (the key enzyme for BH4 production) and ODC1 (the key enzyme for polyamine synthesis). Placental  mRNA levels for GTP-CH1, eNOS, PGF, VEGF, and VEGFR2 increased in response to both 0.4% and 0.8% Arg supplementation. Collectively, these results indicate that dietary Arg supplementation to gilts between days 14 and 25 of pregnancy promotes placental angiogenesis by increasing the expression of mRNAs and proteins for angiogenic factors as well as NO and polyamine syntheses.

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Abbreviations

Arg:

l-arginine

BD:

Becton Dickinson Transduction Laboratories

BH4:

Tetrahydrobiopterin

EPC:

Endothelial precursor cells

GTP-CH1:

GTP cyclohydrolase-I

HPLC:

High-performance liquid chromatography

VEGF:

Vascular endothelial growth factor

NO:

Nitric oxide

cNOS:

Constitutive NO synthase

iNOS:

Inducible NO synthase

eNOS:

Endothelial NO synthase

NOx:

Oxidation end products of NO (nitrite plus nitrate)

ODC1:

Ornithine decarboxylase

PCR:

Polymerase chain reaction

PGF:

Placental growth factor

SPP1:

Secreted phosphoprotein 1

TBST:

Tris-buffered saline-Tween solution

VEGFR1:

Vascular endothelial growth factor receptors 1

VEGFR2:

Vascular endothelial growth factor receptors 2

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Acknowledgements

Agriculture and Food Research Initiative Competitive Grants (2015-67015-23276) from the USDA National Institute of Food and Agriculture supported this work. Data of this study have been presented previously as a poster in the 2018 Society of the Study of Reproduction (SSR)’s Annual Meeting (July 10-13, 2018; New Orleans, LA): Elmetwally MA, Li XL, Johnson GA, Burghardt RC, Herring C, Bazer FW, Wu G. “Dietary supplementation with l-arginine to gilts between days 14 and 25 of gestation enhances placental expression of angiogenic proteins”, P457. The present address of Mohammed A. Elmetwally is Department of Theriogenology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt. The present address of Xilong Li is Institute of Feed Science, The Chinese Academy of Agricultural Sciences, Beijing, China 100081.

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Author notes

  1. Mohammed A. Elmetwally and Xilong Li have contributed equally to this work.

Authors and Affiliations

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

    Mohammed A. Elmetwally, Xilong Li, Cassandra M. Herring, Fuller W. Bazer & Guoyao Wu

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

    Gregory A. Johnson, Robert C. Burghardt & Avery C. Kramer

  3. Medical Physiology, Texas A&M University, College Station, TX, 77843, USA

    Cynthia J. Meininger

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  1. Mohammed A. Elmetwally
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Correspondence to Guoyao Wu.

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Elmetwally, M.A., Li, X., Johnson, G.A. et al. Dietary supplementation with l-arginine between days 14 and 25 of gestation enhances NO and polyamine syntheses and the expression of angiogenic proteins in porcine placentae. Amino Acids 54, 193–204 (2022). https://doi.org/10.1007/s00726-021-03097-2

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