Expression of genes involved in the NF-κB-dependent pathway of the fibrosis in the mare endometrium.
Abstract: Equine endometrosis is a multifactorial chronic degenerative condition, considered to be one of a major causes of equine infertility. The formation of periglandular fibrosis seems to be linked to chronic inflammation of the mare endometrium in a paracrine way and in a response to numerous forms of inflammatory stimuli elicit the net deposition of extracellular matrix (ECM) around the endometrial glands and stroma. We hypothesized some of these stimuli, such as monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and hyaluronan synthases (HASs), may share the nuclear factor-κB (NF-κB) dependent activation pathway. This study aimed to determine whether mRNA expression of MCP-1, IL-6, HASs, and proteins of canonical (RelA/NK-κβ1) and noncanonical (NK-κβ2) signaling pathways for NF-kB would change in subsequent categories of endometrosis during the estrous cycle. The expression of selected genes was established in mare endometrium (n = 80; Kenney and Doig categories I, IIA, IIB, III), obtained in the follicular phase (FLP) and mid-luteal phase (MLP). The high expression of RelA mRNA was observed in III, whereas of NK-κβ1 and NK-κβ2 also in IIA, and IIA and IIB, respectively. The expression of MCP-1 mRNA occurred constantly, regardless of the category, whereas IL-6 mRNA was low in IIA, IIB, and III. The expression of HAS 1 was high in IIA and HAS 3 in IIA, IIB, and III. All those changes were observed in FLP, but not MLP. Our results suggest that NF-κB may be involved in progression of the chronic degenerative condition of the mare endometrium, on both canonical and noncanonical pathways. The most important changes in target genes expression were observed only in FLP, which may suggest the hormone-dependent activation of the NF-κB-dependent fibrosis pathway.
Copyright © 2020. Published by Elsevier Inc.
Publication Date: 2020-01-29 PubMed ID: 32074495DOI: 10.1016/j.theriogenology.2020.01.055Google Scholar: Lookup
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Summary
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This research aims to understand the genetic mechanisms involved in the development of endometrosis, a major cause of infertility in horses. By studying the expressions of certain genes and proteins that might be associated with the disease during different stages of the estrous cycle, the researchers hope to shed more light on how the disease progresses and explore potential therapeutic targets.
Objective of the research
- The researchers aimed to understand the role of the nuclear factor-κB (NF-κB) dependent activation pathway in endometrosis, a chronic degenerative condition of the mare endometrium that is a major cause of equine infertility.
- The study specifically looked at mRNA expression of certain genes and proteins (MCP-1, IL-6, and HASs) believed to be related to NF-κB during various stages of the estrous cycle.
Conduct of the research
- They studied mare endometrium samples from 80 subjects, categorized according to Kenney and Doig’s scale (I, IIA, IIB, III).
- These samples were obtained during two different stages of the estrous cycle: the follicular phase (FLP) and mid-luteal phase (MLP).
Research Findings
- High expression of RelA mRNA – part of the NF-κB pathway – was observed in category III endometrosis.
- For NK-κβ1 and NK-κβ2, also involved in NF-κB signalling, high expression occurred in categories IIA and IIA/IIB respectively.
- Expression of MCP-1 mRNA, linked to inflammation, was constant regardless of the disease category.
- IL-6 mRNA, another inflammation-related gene, had low expression in categories IIA, IIB, and III.
- HAS 1 and 3, genes linked to synthesis of hyaluronan, showed high expression in cats IIA and IIA/IIB/III respectively. These genes are linked to extracellular matrix deposition, a characteristic of fibrosis.
- These changes were all observed in the FLP stage, but not the MLP stage, suggesting hormone-dependent activation of the NF-κB-dependent fibrosis pathway.
Implications of the research
- This study suggests that the NF-κB pathway might be involved in the progressive chronic degeneration seen in endometrosis.
- The most significant changes in target genes expression were observed only in the FLP stage, indicating a potential hormonal influence on the disease’s progression.
- By understanding these mechanisms, new targets for treatment could potentially be identified to help manage the condition and improve fertility rates in horses.
Cite This Article
APA
Domino M, Jasinski T, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Zabielski R, Sady M, Gajewski Z.
(2020).
Expression of genes involved in the NF-κB-dependent pathway of the fibrosis in the mare endometrium.
Theriogenology, 147, 18-24.
https://doi.org/10.1016/j.theriogenology.2020.01.055 Publication
Researcher Affiliations
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland.
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland.
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland.
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, 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 Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland.
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland.
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Veterinary Research Centre and Center for Biomedical Research, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland. Electronic address: zgajewski@supermedia.pl.
MeSH Terms
- Animals
- Estrous Cycle
- Female
- Fibrosis / metabolism
- Fibrosis / veterinary
- Gene Expression Regulation / physiology
- Horse Diseases / metabolism
- Horses
- NF-kappa B / genetics
- NF-kappa B / metabolism
- Uterine Diseases / metabolism
- Uterine Diseases / veterinary
Conflict of Interest Statement
Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper.
Citations
This article has been cited 15 times.- Antar SA, Ashour NA, Marawan ME, Al-Karmalawy AA. Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. Int J Mol Sci 2023 Feb 16;24(4).
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