Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance.
Abstract: Persistent endometritis in the mare is associated with hypersecretion of mucus by endometrial epithelium and migration of neutrophils into the uterine lumen. This study examines the relationships between N-acetylcysteine (NAC), a mucolytic agent with anti-inflammatory properties, and endometrial architecture, serum neutrophil function, post-breeding therapy, and reproductive performance of NAC-treated mares in a clinical setting. In study 1, endometrial biopsies from mares receiving intrauterine saline (fertile-control, n = 6) or 3.3% NAC (fertile-treatment, n = 6; barren-treatment, n = 10) were evaluated by histology and image analysis. In study 2, phagocytic activity of serum-derived neutrophils was measured after adding 0.5% or 3% NAC. In study 3, pregnancy rates of repeat breeders (n = 44) receiving an intrauterine infusion of 3.3% NAC 24-36 hours before mating (group 1) was recorded, as was first cycle of the season pregnancy rates of reproductively normal mares (group 2, n = 85), and mares treated for bacterial endometritis the cycle before mating (group 3, n = 25). Intrauterine NAC did not adversely affect endometrial histology. Extracellular mucus thickness and staining intensity were reduced in fertile-treatment mares (P < 0.03). Neutrophil function was inhibited by 3% NAC solution, but not by 0.5% NAC (P < 0.05). In study 3, for groups 1, 2, and 3, respectively, the first-cycle pregnancy rates were 77%, 74%, and 56%, and early embryonic death rates were 15%, 13%, and 7%. In group 2 mares treated with uterine lavage and oxytocin post-mating, the pregnancy rate was 89% (39/44), whereas in mares treated with uterine lavage and 1 g ceftiofur, it was 60% (24/40). Of the oxytocin-treated mares, 18% (8/44) had ≥ 1 cm of intrauterine fluid or marked uterine edema, whereas 80% (32/40) of the antibiotic-treated mares did. In conclusion, intrauterine infusion of a 3.3% solution of NAC was not irritating and inhibited the oxidative burst of neutrophils. Repeat breeder mares, with evidence of mucus hypersecretion, but no uterine pathogens, when treated with NAC followed by post-mating uterine lavage and oxytocin (and in some cases intrauterine antibiotics), achieved a pregnancy rate of 77%.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication Date: 2013-04-25 PubMed ID: 23623166DOI: 10.1016/j.theriogenology.2013.03.026Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores the effect of N-acetylcysteine (NAC), an agent that reduces mucus and inflammation, on the fertility of mares suffering from a condition called endometritis. Through a series of studies, the research confirmed that NAC doesn’t harm horse uterine tissues, reduces mucus production, slows down neutrophil activity, and enhances fertility rates when accompanied with a regimented post mating treatment.
Study Methodology
In the research, three connected studies were performed:
- Study 1 evaluated biopsy samples of the uterine lining from mares treated with saline solution, as a control group, and a form of NAC.
- Study 2 observed the phagocytic (the process of cells eating bacteria) activity of neutrophils in blood serum after NAC application.
- Study 3 recorded the fertility rates of several groups of mares before and after treatment with NAC and supplementary therapies.
Research Findings
The findings from the research were promising:
- NAC did not cause any harm to the uterine lining of the mares.
- In the NAC-treated group, there was significant reduction in the thickness and staining intensity of extracellular mucus.
- Neutrophil function was found to be reduced by 3% of NAC, whereas reduction was not seen at a concentration of 0.5% .
- The first-attempt pregnancy rates after the NAC treatment were found to be 77% for mares who were repeat breeders, 74% for the reproductively normal mares, and 56% for mares who were treated for bacterial endometritis in the previous cycle.
- The pregnancy rate was 89% for the mares which were given post-coital treatment with uterine lavage and oxytocin; an increase when compared to 60% for those treated with uterine lavage and a gram of ceftiofur.
Conclusion
The researchers concluded that intrauterine infusion of N-acetylcysteine had a positive effect on the fertility rates of mares. Importantly, intrauterine treatments using a 3.3% solution of NAC were not irritating and reduced neutrophil (cells that fight bacteria) activity. The fertility of mares, especially those experiencing mucus overproduction without any uterine pathogens, significantly improved with NAC treatment. Post mating treatments such as uterine lavage and oxytocin also positively contributed to the increased rates of pregnancy.
Cite This Article
APA
Gores-Lindholm AR, LeBlanc MM, Causey R, Hitchborn A, Fayrer-Hosken RA, Kruger M, Vandenplas ML, Flores P, Ahlschwede S.
(2013).
Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance.
Theriogenology, 80(3), 218-227.
https://doi.org/10.1016/j.theriogenology.2013.03.026 Publication
Researcher Affiliations
- Rood and Riddle Equine Hospital, Lexington, Kentuky, USA.
MeSH Terms
- Acetylcysteine / administration & dosage
- Acetylcysteine / pharmacology
- Animals
- Endometritis / drug therapy
- Endometritis / pathology
- Endometritis / veterinary
- Endometrium / drug effects
- Endometrium / pathology
- Female
- Horse Diseases / drug therapy
- Horses
- Neutrophils / drug effects
- Neutrophils / physiology
- Pregnancy
- Reproduction / drug effects
Citations
This article has been cited 4 times.- 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.
- Sakelliou A, Fatouros IG, Athanailidis I, Tsoukas D, Chatzinikolaou A, Draganidis D, Jamurtas AZ, Liacos C, Papassotiriou I, Mandalidis D, Stamatelopoulos K, Dimopoulos MA, Mitrakou A. Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation. Oxid Med Cell Longev 2016;2016:2840643.
- Ferris RA, McCue PM, Borlee GI, Loncar KD, Hennet ML, Borlee BR. In Vitro Efficacy of Nonantibiotic Treatments on Biofilm Disruption of Gram-Negative Pathogens and an In Vivo Model of Infectious Endometritis Utilizing Isolates from the Equine Uterus. J Clin Microbiol 2016 Mar;54(3):631-9.
- Pas D, Oltmanns H, Meißner J. In vitro characterization of antimicrobial efficacy and cytotoxicity of polyvinylpyrrolidone-iodine, N-acetylcysteine, methylglyoxal, and N-chlorotaurine as alternative antimicrobials in treating bovine clinical endometritis. Front Vet Sci 2025;12:1699857.
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