The effect of treatment with immune modulators on endometrial cytokine expression in mares susceptible to persistent breeding-induced endometritis.
Abstract: Research has shown that 6 h after breeding is a critical time during the uterine innate immune response, and the failure to respond appropriately will result in persistent breeding-induced endometritis. This presents a potential opportunity to modulate the course of inflammation towards a timely resolution. Objective: To evaluate the effects of immune modulation on endometrial mRNA expression of inflammatory genes in susceptible mares 6 h after breeding. The hypothesis was that immune modulation alters endometrial cytokine expression in susceptible mares. Methods: A randomised controlled study to evaluate the effects of mycobacterial cell wall extract and dexamethasone on endometrial gene expression after insemination in 6 mares susceptible to persistent breeding-induced endometritis. Methods: Six susceptible mares were selected based on their uterine inflammatory response to insemination. Mares were inseminated during 3 oestrous cycles with 1 × 10(9) nonviable spermatozoa and 1) no additional treatment (control), or in combination with 2) dexamethasone (50 mg i.v.) at the time of insemination, or 3) with mycobacterial cell wall extract (1.5 ml i.v.) administered 24 h prior to insemination. Mares received one treatment per cycle in randomised order, and each mare served as her own control. Endometrial biopsies were collected 6 h after breeding, and quantitative polymerase chain reaction analysis for interleukin (IL)1β, IL6, interferon γ, IL10 and IL1RA was performed. Relative quantification values reported fold changes in mRNA expression from the control. Data were analysed using an ANOVA and significance was set at P<0.05. Results: Expression of IL1β mRNA was lower after treatment with dexamethasone (P<0.001) and mycobacterial cell wall extract (P<0.05) when compared with control. No differences were detected in the mRNA expression of the other cytokines after any of the treatments. Conclusions: Treatment with immune modulators alters endometrial mRNA expression of IL1β after insemination. A better understanding of the mechanisms of immune modulation in the equine uterus can help to improve treatments for persistent breeding-induced endometritis.
© 2014 EVJ Ltd.
Publication Date: 2014-05-08 PubMed ID: 24645833DOI: 10.1111/evj.12266Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates the impact of immune modulators on the gene expression of inflammatory markers in mares susceptible to persistent endometritis following breeding. The results revealed that the use of specific immune modulators could adjust the expression of certain inflammatory genes in the horse’s uterus, offering new insights for potential treatments.
Research Objectives and Hypothesis
The purpose of the study was to assess the effect of immune modulation on the gene expression of inflammatory markers in mares susceptible to persistent breeding-induced endometritis. Specifically, the researchers wanted to analyze the changes 6 hours post-breeding, considered a significant point in the uterine innate immune response. They hypothesized that immune modulation could alter endometrial cytokine expression within this time frame.
Methodology
- The researchers designed and executed a randomised controlled study. They specifically looked at the effects of a mycobacterial cell wall extract and dexamethasone on endometrial gene expression post-insemination.
- Six mares, known to be susceptible to persistent breeding-induced endometritis, were chosen for the study. They were inseminated during three oestrus cycles with nonviable sperm. Alongside this, they were either not treated, treated with dexamethasone at insemination time, or given the mycobacterial cell wall extract 24 hours before insemination. The treatments were randomly ordered and each mare served as her own control.
- Through endometrial biopsies taken 6 hours after breeding, the researchers could analyze the expression of various genes related to inflammation (interleukin [IL]1β, IL6, interferon γ, IL10 and IL1RA) using quantitative polymerase chain reaction analysis.
- The results were processed through an ANOVA and were considered significant if P<0.05.
Results
- The data analysis revealed that the expression of IL1β mRNA decreased post-treatment with dexamethasone or the mycobacterial cell wall extract when compared to the control group. However, there were no detectable changes in the mRNA expression of the other cytokines post any of the treatments.
Conclusions
- The findings of this research suggest that treatment with immune modulators can alter the gene expression of IL1β post insemination. This provides an avenue for further exploration; a more detailed understanding of immune modulation mechanisms within the equine uterus could improve the treatment practices for persistent breeding-induced endometritis.
Cite This Article
APA
Woodward EM, Christoffersen M, Horohov D, Squires EL, Troedsson MH.
(2014).
The effect of treatment with immune modulators on endometrial cytokine expression in mares susceptible to persistent breeding-induced endometritis.
Equine Vet J, 47(2), 235-239.
https://doi.org/10.1111/evj.12266 Publication
Researcher Affiliations
- Department of Veterinary Science, The Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / administration & dosage
- Anti-Inflammatory Agents / pharmacology
- Cell Extracts / administration & dosage
- Cell Extracts / pharmacology
- Cross-Over Studies
- Cytokines / metabolism
- Dexamethasone / administration & dosage
- Dexamethasone / pharmacology
- Endometritis / prevention & control
- Endometritis / veterinary
- Endometrium / drug effects
- Endometrium / metabolism
- Female
- Horse Diseases / etiology
- Horse Diseases / prevention & control
- Horses
- Immunologic Factors / administration & dosage
- Immunologic Factors / pharmacology
- Insemination, Artificial / adverse effects
- Insemination, Artificial / veterinary
- Mycobacterium / cytology
- Polymerase Chain Reaction / methods
- Polymerase Chain Reaction / veterinary
Citations
This article has been cited 10 times.- Ding X, Cui X, Shi J, Cheng X, Yao D, Gao Y, Zhang Y. Construction of a model of endometritis in domestic rabbits using equine-derived pathogens and evaluation of therapeutic effect of sensitive drugs. Front Vet Sci 2023;10:1064522.
- 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).
- Morrell JM, Rocha A. A Novel Approach to Minimising Acute Equine Endometritis That May Help to Prevent the Development of the Chronic State. Front Vet Sci 2021;8:799619.
- Picetti TS, Soveral LF, Miotto R, Erpen LMS, Kreutz Y, Guizzo JA, Frandoloso R, Kreutz LC. Orally administered β-glucan improves the hemolytic activity of the complement system in horses. Vet World 2021 Apr;14(4):835-840.
- Omontese BO, Caixeta LS, Machado VS, Rendahl A, Celestino MLK, Menta PR, Paiva D, Garcia-Muñoz A, Masic A. Effects of the Administration of a Non-specific Immune Stimulant Around Transportation on Health and Performance of Jersey and Jersey-Cross Heifer Calves During the Rearing Period: Randomized Clinical Trial. Front Vet Sci 2020;7:550202.
- 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).
- Crociati M, Capomaccio S, Mandara MT, Stradaioli G, Sylla L, Monaci M, Cappelli K. Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season. BMC Vet Res 2019 Dec 21;15(1):465.
- Nash DM, Paddison J, Davies Morel MCG, Barnea ER. Preimplantation factor modulates acute inflammatory responses of equine endometrium. Vet Med Sci 2018 Nov;4(4):351-356.
- Perrini C, Strillacci MG, Bagnato A, Esposti P, Marini MG, Corradetti B, Bizzaro D, Idda A, Ledda S, Capra E, Pizzi F, Lange-Consiglio A, Cremonesi F. Microvesicles secreted from equine amniotic-derived cells and their potential role in reducing inflammation in endometrial cells in an in-vitro model. Stem Cell Res Ther 2016 Nov 18;7(1):169.
- Marini MG, Perrini C, Esposti P, Corradetti B, Bizzaro D, Riccaboni P, Fantinato E, Urbani G, Gelati G, Cremonesi F, Lange-Consiglio A. Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro. Reprod Biol Endocrinol 2016 Sep 13;14(1):58.
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