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Reproduction in domestic animals = Zuchthygiene2012; 48(4); 554-561; doi: 10.1111/rda.12124

An investigation of uterine nitric oxide production in mares susceptible and resistant to persistent breeding-induced endometritis and the effects of immunomodulation.

Abstract: The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding-induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexamethasone or mycobacterial cell wall extract (MCWE) on uterine NO production and endometrial iNOS mRNA expression. Six susceptible mares were inseminated over three cycles with (i) killed spermatozoa without treatment (control), (ii) killed spermatozoa with 50 mg of dexamethasone IV or (iii) MCWE IV 24 h prior to insemination with killed spermatozoa. Six resistant mares were inseminated with killed spermatozoa as a control. Six hours after breeding, uterine biopsies and secretions were collected and evaluated for NO and iNOS mRNA. In Experiment 1, resistant mares had an increase in iNOS mRNA expression 2 h post-breeding compared to baseline (p = 0.045), 12 h (p = 0.014) and 24 h (p = 0.001). Susceptible mares had higher expression 2 h compared to 6 h (p = 0.046). No differences were observed in mRNA or protein expression of iNOS between resistant and susceptible mares. Resistant mares had a relatively steady amount of total intrauterine NO over 24 h, while susceptible mares had an increase over time, with a significantly higher increase in total NO than resistant mares at 6 (p = 0.04) and 12 h (p = 0.032). In Experiment 2, no differences were observed for iNOS mRNA expression. Susceptible mares had increased NO when compared to resistant mares (p = 0.008) and MCWE decreased NO (p = 0.047).
Publication Date: 2012-12-10 PubMed ID: 23228000DOI: 10.1111/rda.12124Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explores how uterine nitric oxide (NO) production varies in mares susceptible and resistant to persistent breeding-induced endometritis (PBIE), and the effects of certain treatments on this production. The results indicate a differential response to breeding in terms of NO production and expression of inducible NO synthase (iNOS) in resistant and susceptible mares, and the treatments dexamethasone or mycobacterial cell wall extract (MCWE) had varying effects.

Objective and Methodology

  • The researchers’ primary goal was to examine the levels of intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares, either susceptible or resistant to persistent breeding-induced endometritis (PBIE) within 24 hours of mating.
  • 12 mares, half susceptible and half resistant to PBIE, were assessed for uterine secretions and endometrial biopsies collected at different intervals following insemination.
  • The collected materials were examined: uterine secretions for NO and biopsies for iNOS expression.
  • A follow-up experiment involved treating six susceptible mares with either dexamethasone or MCWE before insemination. The mares’ uterine biopsies and secretions were then evaluated for NO and iNOS mRNA.

Findings and Interpretation

  • The study’s results highlighted differences in NO and iNOS expression between mares resilient and susceptible to PBIE post-breeding.
  • Resistant mares displayed an upsurge in iNOS mRNA expression as early as 2 hours following breeding compared to pre-breeding baseline, and this expression was notably higher than documented 12 and 24 hours after mating.
  • Meanwhile, in susceptible mares, iNOS expression peaked 2 hours post-breeding, significantly higher than the 6-hour measure.
  • The research also observed varying patterns between the two mare groups in terms of intrauterine NO: resistant mares had a steady amount over 24 hours, while susceptible mares showed an increase over time. Susceptible mares also recorded significantly higher cumulative NO than resistant mares at the 6 and 12-hour post-breeding measurements.
  • The second experiment with treatments showed no observable changes in iNOS mRNA expression, but susceptible mares had higher NO compared to resistant mares, and the MCWE treatment reduced NO levels.

Conclusion and Implication

  • The research showed that a mare’s susceptibility or resistance to PBIE affects the intrauterine NO and iNOS production following breeding, potentially shaping their reproductive processes and outcomes.
  • Moreover, treatments with dexamethasone or MCWE can alter this NO production, providing a potential avenue for targeted interventions to combat PBIE.

Cite This Article

APA
Woodward EM, Christoffersen M, Campos J, Horohov DW, Scoggin KE, Squires E, Troedsson MH. (2012). An investigation of uterine nitric oxide production in mares susceptible and resistant to persistent breeding-induced endometritis and the effects of immunomodulation. Reprod Domest Anim, 48(4), 554-561. https://doi.org/10.1111/rda.12124

Publication

ISSN: 1439-0531
NlmUniqueID: 9015668
Country: Germany
Language: English
Volume: 48
Issue: 4
Pages: 554-561

Researcher Affiliations

Woodward, E M
  • The Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Christoffersen, M
    Campos, J
      Horohov, D W
        Scoggin, K E
          Squires, E
            Troedsson, M H T

              MeSH Terms

              • Animals
              • Breeding
              • Cell Wall / immunology
              • Dexamethasone / administration & dosage
              • Disease Resistance
              • Disease Susceptibility / immunology
              • Disease Susceptibility / veterinary
              • Endometritis / etiology
              • Endometritis / immunology
              • Endometritis / veterinary
              • Endometrium / enzymology
              • Female
              • Horse Diseases / etiology
              • Horse Diseases / immunology
              • Horses / immunology
              • Horses / metabolism
              • Immunomodulation
              • Insemination, Artificial / veterinary
              • Mycobacterium / immunology
              • Nitric Oxide / biosynthesis
              • Nitric Oxide Synthase Type II / genetics
              • Nitric Oxide Synthase Type II / metabolism
              • Polymerase Chain Reaction / veterinary
              • RNA, Messenger / analysis
              • Uterus / metabolism

              Citations

              This article has been cited 8 times.
              1. Freccero F, Mislei B, Bucci D, Dondi F, Mari G. Effects of Intra-Uterine Fluid Accumulation after Artificial Insemination on Luteal Function in Mares. Animals (Basel) 2022 Dec 23;13(1).
                doi: 10.3390/ani13010067pubmed: 36611677google scholar: lookup
              2. Boni R, Cecchini Gualandi S. Relationship between Oxidative Stress and Endometritis: Exploiting Knowledge Gained in Mares and Cows. Animals (Basel) 2022 Sep 13;12(18).
                doi: 10.3390/ani12182403pubmed: 36139263google scholar: lookup
              3. 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).
                doi: 10.3390/ani12060779pubmed: 35327176google scholar: lookup
              4. Rivera Del Alamo MM, Reilas T, Lukasik K, Galvão AM, Yeste M, Katila T. Inflammatory Markers in Uterine Lavage Fluids of Pregnant, Non-Pregnant, and Intrauterine Device Implanted Mares on Days 10 and 15 Post Ovulation. Animals (Basel) 2021 Dec 8;11(12).
                doi: 10.3390/ani11123493pubmed: 34944269google scholar: lookup
              5. Solano-Suárez G, Caixeta LS, Masic A, Manríquez D, Hatamoto-Zervoudakis L, Paudyal S, Velasquez-Munoz A, Velez J, Pinedo PJ. Effect of peripartal administration of mycobacterium cell wall fraction on health and fertility of Holstein cows under organic-certified management. J Anim Sci 2021 Sep 1;99(9).
                doi: 10.1093/jas/skab191pubmed: 34468760google scholar: lookup
              6. 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).
                doi: 10.3390/ani10122438pubmed: 33352707google scholar: lookup
              7. 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).
                doi: 10.3390/ani10040625pubmed: 32260515google scholar: lookup
              8. 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).
                doi: 10.3390/ijms21041432pubmed: 32093296google scholar: lookup