Nitric oxide stimulates progesterone and prostaglandin E2 secretion as well as angiogenic activity in the equine corpus luteum.
Abstract: Cytokines and nitric oxide (NO) are potential mediators of luteal development and maintenance, angiogenesis, and blood flow. The aim of this study was to evaluate (i) the localization and protein expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) in equine corpora lutea (CL) throughout the luteal phase and (ii) the effect of a nitric oxide donor (spermine NONOate, NONOate) on the production of progesterone (P4) and prostaglandin (PG) E(2) and factor(s) that stimulate endothelial cell proliferation using equine luteal explants. Luteal tissue was classified as corpora hemorrhagica (CH; n = 5), midluteal phase CL (mid-CL; n = 5) or late luteal phase CL (late CL; n = 5). Both eNOS and iNOS were localized in large luteal cells and endothelial cells throughout the luteal phase. The expression of eNOS was the lowest in mid-CL (P < 0.05) and the highest in late CL (P < 0.05). However, no change was found for iNOS expression. Luteal explants were cultured with no hormone added or with NONOate (10(-5) M), tumor necrosis factor-α (TNFα; 10 ng/mL; positive control), or equine LH (100 ng/mL; positive control). Conditioned media by luteal tissues were assayed for P4 and PGE(2) and for their ability to stimulate proliferation of bovine aortic endothelial cells (BAEC). All treatments stimulated release of P4 in CH, but not in mid-CL. TNFα and NONOate treatments also increased PGE(2) levels and BAEC proliferation in CH (P < 0.05). However, in mid-CL, no changes were observed, regardless of the treatments used. These data suggest that NO and TNFα stimulate equine CH secretory functions and the production of angiogenic factor(s). Furthermore, in mares, NO may play a role in CL growth during early luteal development, when vascular development is more intense.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication Date: 2010-09-09 PubMed ID: 20961721DOI: 10.1016/j.domaniend.2010.08.001Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research in this article investigates the influence of nitric oxide on luteal development in horses, specifically looking at progesterone and prostaglandin E2 secretion, as well as angiogenic activity.
Objectives of the Research
- The aim of the study was two-fold. Primarily, the researchers sought to understand the localization and protein expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) in the equine corpus luteum (CL) throughout its luteal phase.
- Additionally, through the use of a nitric oxide donor (spermine NONOate, NONOate), the study aimed to observe the effects on the production of progesterone (P4) and prostaglandin E2 (PGE2), and certain factor(s) that stimulate endothelial cell proliferation in equine luteal explants.
Methodology
- The luteal tissue studied was classified into three types: corpora hemorrhagica (CH), midluteal phase CL (mid-CL), and late luteal phase CL (late CL).
- Both eNOS and iNOS were localized in large luteal cells and endothelial cells throughout the luteal phase, and their expression was observed.
- The luteal explants were then cultured without hormones or with NONOate or tumor necrosis factor-α (TNFα; used as a positive control), or equine luteinizing hormone (LH; also used as a positive control).
- The conditioned media by luteal tissues were assayed for P4 and PGE2, and for their ability to stimulate the proliferation of bovine aortic endothelial cells (BAEC).
Findings
- The study found that all three treatments (NONOate, TNFα, and LH) stimulated the release of progesterone in CH but not in mid-CL.
- The TNFα and NONOate treatments also increased PGE2 levels and BAEC proliferation within the CH.
- However, in mid-CL, no changes in these reponses were noticed, irrespective of the treatments used.
- These results suggest that nitric oxide and TNFα contribute to equine CH by stimulating secretory functions and the production of angiogenic factors.
- Furthermore, in mares, nitric oxide may play a role in corpus luteum growth during early luteal development, when vascular development is more intense.
Cite This Article
APA
Ferreira-Dias G, Costa AS, Mateus L, Korzekwa AJ, Galvão A, Redmer DA, Lukasik K, Szóstek AZ, Woclawek-Potocka I, Skarzynski DJ.
(2010).
Nitric oxide stimulates progesterone and prostaglandin E2 secretion as well as angiogenic activity in the equine corpus luteum.
Domest Anim Endocrinol, 40(1), 1-9.
https://doi.org/10.1016/j.domaniend.2010.08.001 Publication
Researcher Affiliations
- CIISA, Faculdade de Medicina Veterinária, TULisbon, 1300-477 Lisbon, Portugal. gmlfdias@fmv.utl.pt
MeSH Terms
- Animals
- Cattle
- Cell Division
- Corpus Luteum / blood supply
- Corpus Luteum / enzymology
- Corpus Luteum / physiology
- Dinoprostone / biosynthesis
- Dinoprostone / metabolism
- Endothelial Cells / cytology
- Endothelial Cells / enzymology
- Female
- Horses / physiology
- Luteal Cells / enzymology
- Luteal Phase / physiology
- Neovascularization, Physiologic / drug effects
- Nitric Oxide / pharmacology
- Nitric Oxide Donors / pharmacology
- Nitric Oxide Synthase Type II / analysis
- Nitric Oxide Synthase Type III / analysis
- Progesterone / biosynthesis
- Progesterone / metabolism
Citations
This article has been cited 8 times.- Freccero F, Mislei B, Bucci D, Dondi F, Mari G. Effects of Intra-Uterine Fluid Accumulation after Artificial Insemination on Luteal Function in Mares. Animals (Basel) 2022 Dec 23;13(1).
- Wu S, Hu S, Fan W, Zhang X, Wang H, Li C, Deng J. Nitrite exposure may induce infertility in mice. J Toxicol Pathol 2022 Jan;35(1):75-82.
- Zerani M, Polisca A, Boiti C, Maranesi M. Current Knowledge on the Multifactorial Regulation of Corpora Lutea Lifespan: The Rabbit Model. Animals (Basel) 2021 Jan 25;11(2).
- Guerra DD, Hurt KJ. Gasotransmitters in pregnancy: from conception to uterine involution. Biol Reprod 2019 Jul 1;101(1):4-25.
- Galvão A, Tramontano A, Rebordão MR, Amaral A, Bravo PP, Szóstek A, Skarzynski D, Mollo A, Ferreira-Dias G. Opposing roles of leptin and ghrelin in the equine corpus luteum regulation: an in vitro study. Mediators Inflamm 2014;2014:682193.
- Galvão AM, Ferreira-Dias G, Skarzynski DJ. Cytokines and angiogenesis in the corpus luteum. Mediators Inflamm 2013;2013:420186.
- Satué K, La Fauci D, Medica P, Damiá Gímenez E, Cravana C, Fazio E. Shifts between pro-inflammatory and anti-inflammatory profiles in pregnant mares: a review of physiological functions. Front Vet Sci 2025;12:1660759.
- Zhang W, Chen SJ, Guo LY, Zhang Z, Zhang JB, Wang XM, Meng XB, Zhang MY, Zhang KK, Chen LL, Li YW, Wen Y, Wang L, Hu JH, Bai YY, Zhang XJ. Nitric oxide synthase and its function in animal reproduction: an update. Front Physiol 2023;14:1288669.
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