Impairment of the antifibrotic prostaglandin E2 pathway may influence neutrophil extracellular traps-induced fibrosis in the mare endometrium.
Abstract: Prostaglandin E (PGE) has contradictory effects in many organs. It may have proinflammatory, anti-inflammatory, or anti-fibrotic roles, depending on the type of receptors to which it binds. By signaling through its receptors EP2 and EP4, PGE mediates anti-inflammatory and anti-fibrotic actions. In spite of chronic endometrial fibrosis (endometrosis) being a major cause of mare infertility, its pathogenesis is not fully understood. We have shown that contact of mare endometrium in vitro with neutrophil extracellular traps (NETs) proteases favors endometrial collagen type I production. Therefore, we investigated the involvement of the PGE pathway in collagen deposition in mare endometrium, challenged in vitro with proteases present in NETs. Mare endometria (Kenney and Doig categories I/IIA and IIB/III), obtained in the follicular phase (FLP) and mid-luteal phase (MLP), were incubated for 24 h with components found in NETs (elastase, cathepsin-G, and myeloperoxidase). Secretion of PGE and transcripts for specific PGE synthase (PGES) and PGE receptors (EP2 and EP4) were evaluated. Impaired PGE production and low EP2 transcript abundance depended on the endometrial category and estrous cycle phase. Impairment of PGE and/or EP2 might play a role in FLP (category IIB/III) and MLP (I/IIA) endometrial fibrogenesis because of the reduction in its antifibrotic capacity. In conclusion, priming of the endometrium with endogenous ovarian steroids might inhibit the antifibrotic PGE pathway either in healthy or pathologic tissues with collagen formation after NETs proteases action.
Copyright © 2018 Elsevier Inc. All rights reserved.
Publication Date: 2018-11-03 PubMed ID: 30522057DOI: 10.1016/j.domaniend.2018.10.004Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The summary of the research article is: The study investigates the role of the Prostaglandin E2 pathway in the development of endometrial fibrosis in mares, a condition that can lead to infertility. The researchers found that inflammation resulting from neutrophil extracellular traps (NETs) could disrupt this pathway, resulting in increased collagen production and fibrosis.
Research Objectives
- The main aim of the research was to investigate the role of the Prostaglandin E2 (PGE) pathway in collagen deposition and related fibrosis in the mare endometrium. This was done by examining mare endometrial tissue challenged with proteases present in neutrophil extracellular traps (NETs), a response of the immune system that can lead inflammation.
Methodology
- Endometrial tissue samples from mares were obtained in two different phases – the follicular phase (FLP) and mid-luteal phase (MLP). The samples were then exposed to components found in NETs (elastase, cathepsin-G, and myeloperoxidase) for 24 hours.
- After the incubation, the researchers measured the secretion of PGE and the transcripts for specific Prostaglandin E synthase (PGES) and PGE receptors (EP2 and EP4).
Results
- The research showed that there was impaired PGE production and low EP2 transcript abundance, dependent on the endometrial category and estrous cycle phase. This suggested that the PGE pathway might be disrupted in the development of endometrial fibrosis.
Conclusion
- Ultimately, the study concluded that endometrial exposure to endogenous ovarian steroids might inhibit the anti-fibrotic PGE pathway, in both healthy and pathologic tissues. This could lead to increased collagen formation after exposure to NETs proteases, resulting in fibrosis, a distinctive trait of endometrosis.
Cite This Article
APA
Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G.
(2018).
Impairment of the antifibrotic prostaglandin E2 pathway may influence neutrophil extracellular traps-induced fibrosis in the mare endometrium.
Domest Anim Endocrinol, 67, 1-10.
https://doi.org/10.1016/j.domaniend.2018.10.004 Publication
Researcher Affiliations
- Department of Morphology and Function, CIISA- Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Department of Animal Sciences, Coimbra College of Agriculture, Polytechnic Institute of Coimbra, Coimbra, Portugal.
- Department of Morphology and Function, CIISA- Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, Olsztyn, Poland.
- Department of Morphology and Function, CIISA- Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
- Department of Animal Sciences, Coimbra College of Agriculture, Polytechnic Institute of Coimbra, Coimbra, Portugal.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, Olsztyn, Poland.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, Olsztyn, Poland. Electronic address: d.skarzynski@pan.olsztyn.pl.
- Department of Morphology and Function, CIISA- Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
MeSH Terms
- Animals
- Collagen / metabolism
- Dinoprostone / biosynthesis
- Dinoprostone / physiology
- Endometriosis / etiology
- Endometriosis / metabolism
- Endometriosis / veterinary
- Endometrium / chemistry
- Endometrium / metabolism
- Endometrium / pathology
- Estrous Cycle / physiology
- Extracellular Traps / enzymology
- Extracellular Traps / physiology
- Female
- Fibrosis
- Horse Diseases / etiology
- Horse Diseases / pathology
- Horses
- Infertility, Female / etiology
- Infertility, Female / veterinary
- Peptide Hydrolases / metabolism
- Prostaglandin-E Synthases / genetics
- RNA, Messenger / analysis
- Receptors, Prostaglandin E / genetics
- Signal Transduction / drug effects
- Tissue Culture Techniques
Citations
This article has been cited 14 times.- Amaral A, Cebola N, Szóstek-Mioduchowska A, Rebordão MR, Kordowitzki P, Skarzynski D, Ferreira-Dias G. Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium.. Int J Mol Sci 2023 Feb 10;24(4).
- Alpoim-Moreira J, Fernandes C, Rebordão MR, Costa AL, Bliebernicht M, Nunes T, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G. Collagen Type III as a Possible Blood Biomarker of Fibrosis in Equine Endometrium.. Animals (Basel) 2022 Jul 21;12(14).
- Katila T, Ferreira-Dias G. Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares.. Animals (Basel) 2022 Mar 19;12(6).
- Neto da Silva AC, Costa AL, Teixeira A, Alpoim-Moreira J, Fernandes C, Fradinho MJ, Rebordão MR, Silva E, Ferreira da Silva J, Bliebernicht M, Alexandre-Pires G, Ferreira-Dias G. Collagen and Microvascularization in Placentas From Young and Older Mares.. Front Vet Sci 2021;8:772658.
- Amaral A, Fernandes C, Szóstek-Mioduchowska A, Lukasik K, Rebordão MR, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G. The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium.. Life (Basel) 2021 Oct 19;11(10).
- Rebordão MR, Amaral A, Fernandes C, Silva E, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G. Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF(2α) Pathway in the Mare Endometrium.. Animals (Basel) 2021 Sep 6;11(9).
- Amaral A, Fernandes C, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium.. Int J Mol Sci 2021 May 19;22(10).
- 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).
- Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Pinto-Bravo P, Telo da Gama L, Jan Skarzynski D, Ferreira-Dias G. Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions.. Animals (Basel) 2021 Jan 16;11(1).
- Amaral A, Fernandes C, Morazzo S, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. The Inhibition of Cathepsin G on Endometrial Explants With Endometrosis in the Mare.. Front Vet Sci 2020;7:582211.
- Miró J, Gutiérrez-Reinoso M, da Silva JA, Fernandes C, Rebordão MR, Alexandre-Pires G, Catalán J, Ferreira-Dias G. Collagen and Eosinophils in Jenny's Endometrium: Do They Differ With Endometrial Classification?. Front Vet Sci 2020;7:631.
- Szóstek-Mioduchowska A, Leciejewska N, Zelmańska B, Staszkiewicz-Chodor J, Ferreira-Dias G, Skarzynski D. Lysophosphatidic acid as a regulator of endometrial connective tissue growth factor and prostaglandin secretion during estrous cycle and endometrosis in the mare.. BMC Vet Res 2020 Sep 17;16(1):343.
- Lange-Consiglio A, Funghi F, Cantile C, Idda A, Cremonesi F, Riccaboni P. Case Report: Use of Amniotic Microvesicles for Regenerative Medicine Treatment of a Mare With Chronic Endometritis.. Front Vet Sci 2020;7:347.
- Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. The In Vitro Inhibitory Effect of Sivelestat on Elastase Induced Collagen and Metallopeptidase Expression in Equine Endometrium.. Animals (Basel) 2020 May 16;10(5).
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