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.
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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
CIISA, Faculdade de Medicina Veterinária, TULisbon, 1300-477 Lisbon, Portugal. gmlfdias@fmv.utl.pt
Costa, A S
Mateus, L
Korzekwa, A J
Galvão, A
Redmer, D A
Lukasik, K
Szóstek, A Z
Woclawek-Potocka, I
Skarzynski, D J
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).
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).
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.