Use of mesenchymal stem cells or autologous conditioned serum to modulate the inflammatory response to spermatozoa in mares.
Abstract: Current treatments for Persistent mating-induced endometritis such as uterine lavage and oxytocin therapy focus on aiding the uterus in removal of inflammatory products, but these treatments do not modulate the inciting inflammatory response. Biological treatments, such as autologous conditioned serum (ACS) and mesenchymal stem cells (MSCs), have been used in human and veterinary medicine for immunomodulation for over 10 years. The objectives of this project were to evaluate the ability of ACS or MSCs to modulate the inflammatory response to spermatozoa after breeding. Two experiments were performed with six normal mares in each study to evaluate the effects of intrauterine administration of ACS, dexamethasone, or a placebo (experiment 1), or allogeneic MSCs or a placebo (experiment 2) on the inflammatory response to spermatozoa using clinical and biochemical endpoints. Treatment with ACS and MSCs significantly (P < 0.05) reduced the number of neutrophils in the uterine lumen 6 hours after the sperm challenge. An increase (P < 0.05) in the anti-inflammatory cytokine IL-1Ra was observed after treatment with MSCs before exposure to spermatozoa. There was no difference in IL-1Ra concentration in mares treated with ACS, dexamethasone, or a placebo. Mesenchymal stem cells and ACS were able to modulate the immune response to spermatozoa in normal mares. The effect may be due to an increase in IL-1Ra in MSCs-treated mares, but other bioactive molecules may be responsible for the decrease in neutrophils in ACS-treated mares. Autologous conditioned serum and bone-derived culture expanded MSCs were able to modulate the uterine inflammatory response to spermatozoa in normal mares. Treatment with allogeneic stem cells may be beneficial if a similar modulation in inflammatory cytokines occurs in mares affected by persistent mating-induced endometritis.
Published by Elsevier Inc.
Publication Date: 2014-02-27 PubMed ID: 24681213DOI: 10.1016/j.theriogenology.2014.02.015Google Scholar: Lookup
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- Evaluation Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study researched the effectiveness of autologous conditioned serum (ACS) and mesenchymal stem cells (MSCs) in mitigating the inflammatory response to spermatozoa in normal mares. The study found that treatments with ACS and MSCs both lead to significant reductions in neutrophils in the uterine lumen and increased the anti-inflammatory cytokine IL-1Ra.
Objectives of the Study
- The main purpose of this research was to examine whether autologous conditioned serum (ACS) or mesenchymal stem cells (MSCs) had the ability to modulate the inflammatory response to spermatozoa after breeding in mares.
- The study aimed to provide alternative and more effective treatment methods for Persistent Mating-Induced Endometritis, which affects mares.
Methodology
- Two distinct experiments were carried out involving six mares each. The study aimed to evaluate the outcomes of intrauterine administration of ACS, dexamethasone, or a placebo in one experiment, and allogeneic MSCs or a placebo in another.
- The resulting inflammatory response to spermatozoa was measured using both clinical and biochemical endpoints.
Key Findings
- Treatment with both ACS and MSCs significantly (P < 0.05) led to a reduction in the number of neutrophils in the uterine lumen six hours following the sperm challenge.
- An increase in the levels of the anti-inflammatory cytokine IL-1Ra was registered after mares received treatment with MSCs prior to exposure to spermatozoa.
- No difference was observed in IL-1Ra concentration when the mares were treated with ACS, dexamethasone, or a placebo.
- ACS and MSCs were reported to be capable of controlling the immune response to spermatozoa in normal mares, an effect that could be attributed to the increase in IL-1Ra in the mares treated with MSCs.
Conclusions and Implications
- The study concluded that both autologous conditioned serum (ACS) and bone-derived culture expanded MSCs succeeded in regulating the uterine inflammatory response to spermatozoa in normal mares.
- The research suggests that treatment with allogeneic stem cells may prove beneficial if there is a similar modulation in inflammatory cytokines in mares suffering from persistent mating-induced endometritis.
Cite This Article
APA
Ferris RA, Frisbie DD, McCue PM.
(2014).
Use of mesenchymal stem cells or autologous conditioned serum to modulate the inflammatory response to spermatozoa in mares.
Theriogenology, 82(1), 36-42.
https://doi.org/10.1016/j.theriogenology.2014.02.015 Publication
Researcher Affiliations
- Equine Reproduction Laboratory, Colorado State University, Fort Collins Colorado USA. Electronic address: rferris@colostate.edu.
- Orthopaedic Research Center, Colorado State University, Fort Collins Colorado USA.
- Equine Reproduction Laboratory, Colorado State University, Fort Collins Colorado USA.
MeSH Terms
- Animals
- Breeding / methods
- Dexamethasone / therapeutic use
- Endometritis / prevention & control
- Female
- Horses / physiology
- Immunosuppression Therapy
- Male
- Mesenchymal Stem Cell Transplantation
- Spermatozoa / immunology
Citations
This article has been cited 11 times.- Lange-Consiglio A, Gaspari G, Funghi F, Capra E, Cretich M, Frigerio R, Bosi G, Cremonesi F. Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis. Int J Mol Sci 2023 Mar 8;24(6).
- Uberti B, Plaza A, Henríquez C. Pre-conditioning Strategies for Mesenchymal Stromal/Stem Cells in Inflammatory Conditions of Livestock Species. Front Vet Sci 2022;9:806069.
- Cequier A, Sanz C, Rodellar C, Barrachina L. The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses. Animals (Basel) 2021 Mar 25;11(4).
- 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.
- Schöniger S, Schoon HA. The Healthy and Diseased Equine Endometrium: A Review of Morphological Features and Molecular Analyses. Animals (Basel) 2020 Apr 5;10(4).
- 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).
- Rezaei F, Moazzeni SM. Comparison of The Therapeutic Effect of Syngeneic, Allogeneic, and Xenogeneic Adipose Tissue-Derived Mesenchymal Stem Cells on Abortion Rates in A Mouse Model. Cell J 2019 Apr;21(1):92-98.
- Lara E, Rivera N, Cabezas J, Navarrete F, Saravia F, Rodríguez-Alvarez L, Castro FO. Endometrial Stem Cells in Farm Animals: Potential Role in Uterine Physiology and Pathology. Bioengineering (Basel) 2018 Sep 18;5(3).
- Rink BE, Beyer T, French HM, Watson E, Aurich C, Donadeu FX. The Fate of Autologous Endometrial Mesenchymal Stromal Cells After Application in the Healthy Equine Uterus. Stem Cells Dev 2018 Aug 1;27(15):1046-1052.
- Alfatlawy HJ. Microbial profile of post-breeding endometritis in Arabian mares from the Al-Hira District, Iraq. Open Vet J 2025;15(8):3670-3676.
- Del Prete C, Attolini E, Merlo B, Iacono E, Nocera FP, De Martino L, Longobardi C, Damiano S, Longobardi V, Cocchia N, Pasolini MP. Post-Insemination Infusion of Wharton's Jelly Mesenchymal Stromal/Stem Cells-Derived Conditioned Medium: A Novel Approach for Improving Pregnancy Outcomes in Problem Mares. Vet Sci 2025 May 16;12(5).
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