Effects of oral treatment with N-acetylcysteine on the viscosity of intrauterine mucus and endometrial function in estrous mares.
Abstract: Persistent breeding-induced endometritis is ranked as the third most common medical problem in the adult mare and leads to enormous economic loss in horse breeding. In mares suffering from persistent breeding-induced endometritis, increased amounts of intrauterine (i.u.) fluid or viscous mucus in estrus or after breeding may act as a barrier for sperm and can contribute to low fertility. Current therapies of these mares aim to eliminate i.u. fluid and mucus by uterine lavage and/or administration of ecbolic drugs. Recently, i.u. administration of N-acetylcysteine (NAC) has been shown to support therapy in mares with endometritis. It was the objective of the present study to investigate effects of an oral administration of NAC on the viscosity of i.u. fluid in estrous mares. It was hypothesized that oral treatment with NAC reduces the viscosity of i.u. fluid and has a positive effect on the inflammatory response of the endometrium. Mares (n = 12) were included in the study as soon as estrus was detected (ovarian follicle >3.0 cm and endometrial edema), which was defined as Day 1. They were randomly assigned to a treatment (10 mg/kg NAC on Days 1-4) or a control group (no treatment). On days 1 and 5 i.u. mucus was collected and its rheologic properties were accessed. On Day 5, endometrial biopsies were obtained and evaluated for integrity of the luminal epithelium, number of polymorphonuclear neutrophils (PMN), staining for cyclooxygenase 2 (COX2), staining with Kiel 67 antigen (Ki-67), lectins and periodic acid Schiff (PAS). In the treatment group, viscosity of i.u. mucus increased significantly between Days 1 and 5 (P < 0.05), while no differences were found in control mares (n.s.). At no time were significant differences between treated and control mares seen. Integrity of epithelium was not affected. After NAC treatment the mean number of PMN in endometrial biopsies was significantly lower compared to mares of the control group (1.9 ± 0.3 vs. 4.8 ± 0.4; P < 0.05). Nuclear immunostaining for COX2 was significantly lower after NAC treatment compared to control mares (P < 0.05). Score for PAS and Alcain staining of mucus in deep uterine glands differed significantly between groups (both P < 0.05). We conclude that oral NAC treatment does not reduce viscosity of uterine mucus but has an antiinflammatory effect on the equine endometrium.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication Date: 2012-07-21 PubMed ID: 22819282DOI: 10.1016/j.theriogenology.2012.05.013Google Scholar: Lookup
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Summary
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This research analyses the impact of oral N-acetylcysteine (NAC) treatment on the thickness of fluid in the uterus (intrauterine fluid) and the functioning of the uterus lining in female horses when they are in heat. The researchers hypothesized that NAC intake would decrease the fluid’s viscidity and positively impact the inflammation response in the uterus’ lining.
Study Objective and Background
- This study aimed to investigate how administering NAC orally affects the thickness of intrauterine fluid in mares (female horses) when they are in estrus (in heat).
- Implications of the research highlight the potential solution for chronic endometritis in horses (a common medical issue in adult mares triggered by breeding, resulting in notable economic loss in the breeding sector). Increased level of intrauterine fluids or viscous mucus after breeding or being in heat may prevent the sperm from reaching the egg, leading to fertility issues.
- The study also aimed to understand whether NAC has any effect on the inflammation response in the endometrium (uterine wall), as present therapies for affected mares focus on eliminating this fluid or mucus via uterine lavage (washing out the uterus) and/or ecbolic drugs (substances that stimulate uterine contractions).
- In previous studies, NAC had shown supportive effects in therapeutically treating mares with endometritis when administered intrauterinely. Therefore, researchers wanted to see if similar results could be achieved with oral administration.
Method
- 12 mares, just entering into estrus, were selected and segregated randomly to the treatment group (receive 10mg/kg NAC from Day1 to Day4) and the control group.
- Throughout the study, the intrauterine mucus was observed for its rheologic (flow) properties, and on Day 5, endometrial biopsies were done to assess the state of the inner uterine lining.
- The biopsies were evaluated for multiple factors including the epithelium’s integrity, the count of polymorphonuclear neutrophils (PMN, type of white blood cells), cyclooxygenase 2 (COX2, an enzyme involved in inflammation) staining, and Kiel 67 antigen (Ki-67, a protein related to cell proliferation) staining. The mucus in deep uterine glands was also stained and evaluated.
Results and Conclusion
- The results showed a significant increase in the intrauterine mucus’s viscosity in the mares who received NAC treatment, contradicting the original hypothesis.
- Contrarily, the NAC treatment significantly lowered the PMN count in the endometrial biopsies, implying less inflammation in the endometrium.
- There was marked decrease in COX2, suggesting less inflammation after NAC treatment.
- The researchers concluded that while oral NAC treatment did not reduce the viscosity of uterine mucus (unlike intrauterine administration), it did have an observable and beneficial anti-inflammatory effect on the equine endometrium.
Cite This Article
APA
Witte TS, Melkus E, Walter I, Senge B, Schwab S, Aurich C, Heuwieser W.
(2012).
Effects of oral treatment with N-acetylcysteine on the viscosity of intrauterine mucus and endometrial function in estrous mares.
Theriogenology, 78(6), 1199-1208.
https://doi.org/10.1016/j.theriogenology.2012.05.013 Publication
Researcher Affiliations
- Clinic for Animal Reproduction, Freie Universität, Berlin, Germany.
MeSH Terms
- Acetylcysteine / administration & dosage
- Animals
- Anti-Inflammatory Agents / administration & dosage
- Body Fluids / drug effects
- Body Fluids / physiology
- Breeding
- Endometritis / etiology
- Endometritis / prevention & control
- Endometritis / veterinary
- Endometrium / chemistry
- Endometrium / drug effects
- Endometrium / physiology
- Female
- Horse Diseases / etiology
- Horse Diseases / prevention & control
- Horses / physiology
- Immunohistochemistry
- Ki-67 Antigen / analysis
- Lectins / metabolism
- Mucus / drug effects
- Mucus / physiology
- Uterus
- Viscosity / drug effects
Citations
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