Impairment of the interleukin system in equine endometrium during the course of endometrosis.
Abstract: The aim of the study was to characterize endometrial mRNA transcription, immunolocalization, and protein expression of interleukin (IL) 1alpha, IL1beta, IL6, and IL1RI, IL1RII, and IL6Ralpha/beta in the course of endometrosis during the estrous cycle. Additionally, the influence of IL1alpha, IL1beta, and IL6 on prostaglandin (PG) secretion and PG synthase mRNA transcription in endometrial tissue during endometrosis was investigated. The endometrial samples were obtained at the early (n = 12), mid- (n = 12), and late (n = 12) luteal phases and at the follicular (n = 12) phase of the estrous cycle. Within each of these phases, there were four samples within each category I, II, and III of endometrium, according to the Kenney classification. In experiment 1, transcription of IL1alpha, IL1beta, IL6, and their receptor's (IL1RI, IL1RII, and IL6Ralpha/beta) mRNAs and their immunolocalization and protein expression were determined using real-time PCR and immunohistochemistry, respectively. In Experiment 2, endometrial samples (n = 5 samples within categories I, II, and III) were obtained for tissue culture in the midluteal phase of the estrous cycle. The endometrial tissues were stimulated with IL1alpha (10 ng/ml), IL1beta (10 ng/ml), IL6 (10 ng/ml), and oxytocin (positive control; 10⁻⁷ M) for 24 h. The PG concentration was determined using ELISA. In addition, transcription of PTGS-2, PGES, and PGFS mRNAs was determined using real-time PCR. ILs were found to regulate PG secretion via modulation of PG synthases in equine endometrium. The alterations in IL and the expression of their receptors, and in endometrial secretory functions, were observed during the course of endometrosis, and suggest serious changes in the endometrial microenvironment. The described disturbances may be closely related to impaired endometrial processes responsible for the subfertility or the infertility in endometrosis.
Publication Date: 2013-10-04 PubMed ID: 23946535DOI: 10.1095/biolreprod.113.109447Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research focuses on how the interleukin system, which is part of the immune system, is affected in horse uteruses during endometrosis, a common disease of the uterine lining that can lead to infertility. Techniques such as PCR and immunohistochemistry were used to identify changes in immune signaling proteins and related genes during different phases of the reproductive cycle. The study found that endometrosis alters the expression of these immune-related factors, suggesting changes in the uterine immune environment that may be associated with fertility problems in horses with endometrosis.
Objectives and Methods
- The study aimed to understand how specific interleukin proteins (IL1alpha, IL1beta and IL6) and their receptors (IL1RI, IL1RII and IL6Ralpha/beta), which play major roles in immune response, change in the horse uterine lining in endometrosis during different stages of the estrous cycle.
- The researchers also investigated how these interleukins affect the production of prostaglandins, chemicals that perform key functions in the uterus, including regulation of inflammation and tissue changes during the menstrual cycle.
- To do this, they collected samples of uterine lining at early, middle and late luteal phases and at the follicular phase of the estrous cycle. They used techniques such as real-time PCR for analyzing gene expression and immunohistochemistry for visualizing protein distribution.
Experiments and Findings
- In the first experiment, researchers assessed gene and protein expression of the mentioned interleukins and their receptors.
- In the second experiment, endometrial tissue samples were placed in culture and stimulated with the interleukins to observe prostaglandin secretion and the expression of genes related to prostaglandin synthesis.
- The study found that interleukins regulate prostaglandin secretion by controlling the expression of prostaglandin synthase enzymes.
- Also, alterations in the expression of interleukins and their receptors were noted during endometrosis, suggesting changes in the uterine microenvironment which could impact fertility.
Implications
- This research contributes to a better understanding of the complexities of the immune response in the uterus during endometrosis. The changes observed may indicate disruption in key endometrial processes leading to subfertility or infertility.
- The interleukins and their receptors could potentially be used as biomarkers to determine disease progression in endometrosis or to develop new treatment strategies for fertility issues associated with this disease.
Cite This Article
APA
Szóstek AZ, Lukasik K, Galvão AM, Ferreira-Dias GM, Skarzynski DJ.
(2013).
Impairment of the interleukin system in equine endometrium during the course of endometrosis.
Biol Reprod, 89(4), 79.
https://doi.org/10.1095/biolreprod.113.109447 Publication
Researcher Affiliations
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Olsztyn, Poland.
MeSH Terms
- Abattoirs
- Animals
- Cyclooxygenase 2 / biosynthesis
- Cyclooxygenase 2 / genetics
- Cyclooxygenase 2 / metabolism
- Endometrium / immunology
- Endometrium / metabolism
- Endometrium / pathology
- Estrous Cycle
- Female
- Gene Expression Regulation, Developmental
- Horse Diseases / immunology
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horse Diseases / physiopathology
- Horses
- Hydroxyprostaglandin Dehydrogenases / biosynthesis
- Hydroxyprostaglandin Dehydrogenases / genetics
- Hydroxyprostaglandin Dehydrogenases / metabolism
- Immunohistochemistry / veterinary
- Interleukins / biosynthesis
- Interleukins / genetics
- Interleukins / metabolism
- Intramolecular Oxidoreductases / biosynthesis
- Intramolecular Oxidoreductases / genetics
- Intramolecular Oxidoreductases / metabolism
- Prostaglandin-E Synthases
- Prostaglandins / metabolism
- RNA, Messenger / metabolism
- Receptors, Interleukin / biosynthesis
- Receptors, Interleukin / genetics
- Receptors, Interleukin / metabolism
- Severity of Illness Index
- Signal Transduction
- Tissue Culture Techniques / veterinary
- Uterine Diseases / immunology
- Uterine Diseases / metabolism
- Uterine Diseases / pathology
- Uterine Diseases / veterinary
Citations
This article has been cited 24 times.- Zdrojkowski Ł, Jasiński T, Ferreira-Dias G, Pawliński B, Domino M. The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review. Int J Mol Sci 2023 Feb 2;24(3).
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- 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).
- 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).
- Wojtysiak K, Ryszka W, Stefaniak T, Król J, Kozdrowski R. Changes in the Secretion of Anti-Inflammatory Cytokines and Acute-Phase Proteins in the Uterus after Artificial Insemination in the Mare. Animals (Basel) 2020 Dec 19;10(12).
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- 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).
- Canisso IF, Segabinazzi LGTM, Fedorka CE. Persistent Breeding-Induced Endometritis in Mares - a Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology. Int J Mol Sci 2020 Feb 20;21(4).
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- Siemieniuch MJ, Szóstek AZ, Gajos K, Kozdrowski R, Nowak M, Okuda K. Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares. PLoS One 2016;11(5):e0154934.
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- Sadowska A, Molcan T, Słyszewska M, Skarzynski DJ, Ferreira-Dias G, Szóstek-Mioduchowska A. Transcriptomic Insights into Tumor Necrosis Factor α's Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts. Int J Mol Sci 2025 Nov 24;26(23).
- Wójtowicz A, Sadowska A, Molcan T, Słyszewska M, Drzewiecka EM, Tobolski D, Ferreira-Dias G, Szóstek-Mioduchowska A. Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts. Sci Rep 2025 Oct 16;15(1):36263.
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- Drzewiecka EM, Molcan T, Sadowska A, Piotrowska-Tomala K, Słyszewska M, Dias GF, Skarżyński DJ, Szóstek-Mioduchowska A. The myometrial transcriptome changes in mares with endometrosis. Sci Rep 2025 Jan 25;15(1):3173.
- Piotrowska-Tomala KK, Szóstek-Mioduchowska A, Jonczyk AW, Drzewiecka EM, Wrobel MH, Hojo T, Ferreira-Dias G, Skarzynski DJ. The effect of lysophosphatidic acid on myometrial contractility and the mRNA transcription of its receptors in the myometrium at different stages of endometrosis in mares. BMC Vet Res 2024 Dec 19;20(1):571.
- Wong YS, Mançanares AC, Navarrete F, Poblete P, Mendez-Pérez L, Cabezas J, Riadi G, Rodríguez-Alvarez L, Castro FO. Extracellular vesicles secreted by equine adipose mesenchymal stem cells preconditioned with transforming growth factor β-1 are enriched in anti-fibrotic miRNAs and inhibit the expression of fibrotic genes in an in vitro system of endometrial stromal cells fibrosis. Vet Q 2024 Dec;44(1):1-11.
- Wong YS, Mançanares AC, Navarrete FI, Poblete PM, Méndez-Pérez L, Ferreira-Dias GML, Rodriguez-Alvarez L, Castro FO. Mare stromal endometrial cells differentially modulate inflammation depending on oestrus cycle status: an in vitro study. Front Vet Sci 2023;10:1271240.
- Szóstek-Mioduchowska A, Wójtowicz A, Sadowska A, Moza Jalali B, Słyszewska M, Łukasik K, Gurgul A, Szmatoła T, Bugno-Poniewierska M, Ferreira-Dias G, Skarzynski DJ. Transcriptomic profiling of mare endometrium at different stages of endometrosis. Sci Rep 2023 Sep 27;13(1):16263.
- Wójtowicz A, Molcan T, Lukasik K, Żebrowska E, Pawlina-Tyszko K, Gurgul A, Szmatoła T, Bugno-Poniewierska M, Ferreira-Dias G, Skarzynski DJ, Szóstek-Mioduchowska A. The potential role of miRNAs and regulation of their expression in the development of mare endometrial fibrosis. Sci Rep 2023 Sep 24;13(1):15938.
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