Equine luteal function regulation may depend on the interaction between cytokines and vascular endothelial growth factor: an in vitro study.
Abstract: We hypothesized that cytokines influence luteal angiogenesis in mares, while angiogenic factors themselves can also regulate luteal secretory capacity. Therefore, the purpose of this study was to evaluate the role of cytokines--tumor necrosis factor alpha (TNF), interferon gamma (IFNG) and Fas ligand (FASL)--on in vitro modulation of angiogenic activity and mRNA level of vascular endothelial growth factor A (VEGF), its receptor VEGFR2, thrombospondin 1 (TSP1), and its receptor CD36 in equine corpus luteum (CL) throughout the luteal phase. After treatment, VEGF protein expression was determined in midluteal phase (mid) CL cells. The role of VEGF on regulation of luteal secretory capacity was assessed by progesterone (P(4)) and prostaglandin E(2) (PGE(2)) production and by mRNA levels for steroidogenic enzymes 3-beta-hydroxysteroid dehydrogenase (3betaHSD) and PGE synthase (PGES). In early CL cells, TNF increased angiogenic activity (bovine aortic endothelial cell viability) and VEGF and VEGFR2 mRNA levels and decreased CD36 (real-time PCR relative quantification). In mid-CL cells, TNF increased VEGF mRNA and protein expression (Western blot analysis) and reduced CD36 mRNA levels, while FASL and TNF+IFNG+FASL decreased VEGF protein expression. In late CL cells, TNF and TNF+IFNG+FASL reduced VEGFR2 mRNA, but TNF+IFNG+FASL increased TSP1 and CD36 mRNA. VEGF treatment increased mRNA levels of 3betaHSD and PGES and secretion of P(4) and PGE(2). In conclusion, these findings suggest a novel auto/paracrine action of cytokines, specifically TNF, on the up-regulation of VEGF for angiogenesis stimulation in equine early CL, while at luteolysis, cytokines down-regulated angiogenesis. Additionally, VEGF stimulated P(4) and PGE(2) production, which may be crucial for CL establishment.
Publication Date: 2012-06-22 PubMed ID: 22492973DOI: 10.1095/biolreprod.111.097147Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The study suggests that cytokines, specifically tumor necrosis factor alpha (TNF), and vascular endothelial growth factor A (VEGF), potentially play an regulating role in equine luteal function, by modulating angiogenic activity and hormone secretion. This interaction appears to be crucial for the establishment and cycle of the equine corpus luteum (CL).
Research Objective
- The purpose of this research was to examine the relationship between cytokines and angiogenic activity in mares. In particular, the researchers sought to determine if cytokines are able to influence the progress of luteal angiogenesis and if angiogenic factors contribute to luteal secretory capacity.
Methodology
- Researchers used different stages of equine CL cells to test the effect of cytokines, such as TNF, interferon gamma (IFNG), and Fas ligand (FASL) on the modulation of angiogenic activity and mRNA level of VEGF, its receptor VEGFR2, thrombospondin 1 (TSP1), and its receptor CD36.
- They also analyzed the role of VEGF on the regulation of luteal secretory capacity by observing the production of progesterone (P4) and prostaglandin E2 (PGE2), as well as the mRNA levels for steroidogenic enzymes.
Key Findings
- In early CL cells, TNF increased the viability of bovine aortic endothelial cells, enhanced the mRNA levels of VEGF and VEGFR2, and diminished those of CD36.
- In mid-CL cells, TNF increased the mRNA and protein expression of VEGF, while decreasing the mRNA levels of CD36. Meanwhile, FASL and a combination of TNF, IFNG and FASL decreased VEGF protein expression.
- In later CL phases, TNF and the combination of cytokines reduced VEGFR2 mRNA levels, while a combination of TNF, IFNG and FASL increased the mRNA levels of TSP1 and CD36.
- VEGF treatment boosted mRNA levels of 3betaHSD, PGES and the secretion of P4 and PGE2.
- These findings suggest a novel auto/paracrine regulatory action of cytokines, specifically TNF, on the up-regulation of VEGF to stimulate angiogenesis in early equine CL. In the luteolysis phase, the cytokines repressed angiogenesis.
- Furthermore, VEGF stimulated the production of P4 and PGE2, which may be fundamental for the establishment of the corpus luteum (CL).
Cite This Article
APA
Galvão A, Henriques S, Pestka D, Lukasik K, Skarzynski D, Mateus LM, Ferreira-Dias GM.
(2012).
Equine luteal function regulation may depend on the interaction between cytokines and vascular endothelial growth factor: an in vitro study.
Biol Reprod, 86(6), 187.
https://doi.org/10.1095/biolreprod.111.097147 Publication
Researcher Affiliations
- CIISA, Faculty of Veterinary Medicine, Technical University of Lisbon, Lisbon, Portugal.
MeSH Terms
- 3-Hydroxysteroid Dehydrogenases / metabolism
- Animals
- CD36 Antigens / metabolism
- Cells, Cultured
- Corpus Luteum / metabolism
- Cytokines / metabolism
- Dinoprostone / metabolism
- Female
- Horses / metabolism
- Intramolecular Oxidoreductases / metabolism
- Luteal Phase / metabolism
- Neovascularization, Physiologic
- Progesterone / metabolism
- Prostaglandin-E Synthases
- RNA, Messenger / metabolism
- Thrombospondins / metabolism
- Vascular Endothelial Growth Factor A / metabolism
- Vascular Endothelial Growth Factor Receptor-2 / metabolism
Citations
This article has been cited 13 times.- Sharma Y, Galvão AM. Maternal obesity and ovarian failure: is leptin the culprit?. Anim Reprod 2022;19(4):e20230007.
- Piotrowska-Tomala KK, Jonczyk AW, Szóstek-Mioduchowska AZ, Żebrowska E, Ferreira-Dias G, Skarzynski DJ. The Effects of Prostaglandin E(2) Treatment on the Secretory Function of Mare Corpus Luteum Depends on the Site of Application: An in vivo Study.. Front Vet Sci 2021;8:753796.
- Adamowski M, Wołodko K, Oliveira J, Castillo-Fernandez J, Murta D, Kelsey G, Galvão AM. Leptin Signaling in the Ovary of Diet-Induced Obese Mice Regulates Activation of NOD-Like Receptor Protein 3 Inflammasome.. Front Cell Dev Biol 2021;9:738731.
- McIntosh SZ, Quinn KE, Ashley RL. CXCL12 May Drive Inflammatory Potential in the Ovine Corpus Luteum During Implantation.. Reprod Sci 2022 Jan;29(1):122-132.
- Pinto-Bravo P, Rebordão MR, Amaral A, Fernandes C, Galvão A, Silva E, Pessa-Santos P, Alexandre-Pires G, Roberto da Costa RP, Skarzynski DJ, Ferreira-Dias G. Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct.. Animals (Basel) 2021 Apr 12;11(4).
- Walewska E, Wołodko K, Skarzynski D, Ferreira-Dias G, Galvão A. The Interaction Between Nodal, Hypoxia-Inducible Factor 1 Alpha, and Thrombospondin 1 Promotes Luteolysis in Equine Corpus Luteum.. Front Endocrinol (Lausanne) 2019;10:667.
- Olfert IM. Physiological Capillary Regression is not Dependent on Reducing VEGF Expression.. Microcirculation 2016 Feb;23(2):146-56.
- Sano M, Hashiba K, Nio-Kobayashi J, Okuda K. The luteotrophic function of galectin-1 by binding to the glycans on vascular endothelial growth factor receptor-2 in bovine luteal cells.. J Reprod Dev 2015;61(5):439-48.
- Fair T. The contribution of the maternal immune system to the establishment of pregnancy in cattle.. Front Immunol 2015;6:7.
- 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.
- Osz K, Ross M, Petrik J. The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis.. Reprod Biol Endocrinol 2014 Mar 14;12:21.
- Galvão AM, Ferreira-Dias G, Skarzynski DJ. Cytokines and angiogenesis in the corpus luteum.. Mediators Inflamm 2013;2013:420186.
- Boutzios G, Karalaki M, Zapanti E. Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility.. Endocrine 2013 Apr;43(2):314-7.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
