Dose-dependent inhibition of uterine contractility by nitric oxide: A potential mechanism underlying persistent breeding-induced endometritis in the mare.
Abstract: Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4-19 years; body weight 405-530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and presence of any apparent abnormality. After euthanasia, one uterine tissue sample was collected for histological evaluation and four full-thickness uterine tissue strips (10-12 mm × 2 mm), two parallel to each muscle layer, were excised for in-vitro contractility evaluation. Strips were suspended in tissue chambers containing Krebs-Henseleit solution, with continuous aeration (95% O-5% CO; pH 7.4) at 37 °C. After equilibration, spontaneous contractility was recorded (pre-treatment) and strips excised in each direction were randomly allocated to each of two groups: 1) SNAP (S-nitroso-N-acetylpenicillamine, an NO donor); or 2) NAP (N-acetyl-d-penicillamine, vehicle and time-matched control). These were treated at 15 min intervals with increasing concentrations (10 M to 10 M) of SNAP and NAP, respectively. Contractility data was recorded throughout the experiment. An interaction effect of group-by-concentration was observed (P 8 years compared to mares aged ≤ 8 years). In conclusion, results of this study indicate that NO has a dose-dependent inhibitory effect on spontaneous uterine contractility irrespective of the muscle layer in the mare.
Copyright © 2017 Elsevier Inc. All rights reserved.
Publication Date: 2016-11-28 PubMed ID: 28166989DOI: 10.1016/j.theriogenology.2016.11.026Google Scholar: Lookup
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- Journal Article
Summary
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This paper investigates the role nitric oxide (NO) could play in prolonged breeding-induced endometritis in mares, discovering its potential inhibitory impact on uterine contractility.
Introduction and Objectives
- The research aims to understand whether nitric oxide (NO) interferes with the uterine contractions in mares, which could potentially cause persistent breeding-induced endometritis—a condition characterized by inflammation of the uterine lining.
- The team planned to examine in-vitro effects of NO on uterine contractility, assess if there were differences in NO’s effects between the longitudinal and circular muscle layers of the uterus. They also aimed to analyze the variables of age, stage of cycle, and muscle layer to determine their potential influences on the research results.
Methodology
- The researchers first did a transrectal examination of the reproductive tract of eight non-pregnant mares of different ages and weights before euthanasia.
- From each mare, a sample was collected for histological evaluation. Additionally, four full-thickness uterine tissue strips, two parallel to each muscle layer, were used for in-vitro contractility examination.
- These strips were placed in tissue chambers filled with a solution called Krebs-Henseleit, which was continuously aerated and kept at the temperature of 37 °C. The spontaneous contractility of the strips was recorded and labeled as pre-treatment.
- The strips were then parted into two groups, one treated with SNAP and other with NAP after every 15 minutes at increasing concentrations. SNAP being a nitric oxide donor, NAP acted as a control.
- The researchers kept a record of the contractility data throughout the experiment.
Results
- It was observed that significant interactional effects were seen, with mean contractility significantly lower post-treatment with 10 M and 10 M SNAP compared to pre-treatment contractility.
- The control group did not show significant differences in contractility.
- Secondary findings revealed that age, stage of the estrous cycle and uterine histology grade all had significant main effects in the experimental results. For instance, mares over 8 years old exhibited lower contractility compared to younger mares.
Conclusion
- The study confirmed that NO does play a role in inhibiting spontaneous uterine contractility, and this effect is dose-dependent and consistent across different muscle layers of the mare’s uterus.
Cite This Article
APA
Khan FA, Chenier TS, Murrant CL, Foster RA, Hewson J, Scholtz EL.
(2016).
Dose-dependent inhibition of uterine contractility by nitric oxide: A potential mechanism underlying persistent breeding-induced endometritis in the mare.
Theriogenology, 90, 59-64.
https://doi.org/10.1016/j.theriogenology.2016.11.026 Publication
Researcher Affiliations
- Department of Population Medicine, University of Guelph, Canada. Electronic address: firdous@uoguelph.ca.
- Department of Population Medicine, University of Guelph, Canada.
- Department of Human Health and Nutritional Sciences, University of Guelph, Canada.
- Department of Pathobiology, University of Guelph, Canada.
- Department of Clinical Studies, University of Guelph, Canada.
- Department of Population Medicine, University of Guelph, Canada.
MeSH Terms
- Animals
- Dose-Response Relationship, Drug
- Endometritis / etiology
- Endometritis / physiopathology
- Endometritis / veterinary
- Female
- Horse Diseases / etiology
- Horse Diseases / physiopathology
- Horses / physiology
- Myometrium / drug effects
- Myometrium / physiopathology
- Nitric Oxide / metabolism
- Nitric Oxide Donors / pharmacology
- Penicillamine / analogs & derivatives
- Penicillamine / pharmacology
- Pregnancy
- S-Nitroso-N-Acetylpenicillamine / pharmacology
- Uterine Contraction / drug effects
- Uterus / drug effects
- Uterus / physiopathology
Citations
This article has been cited 4 times.- 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).
- 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).
- 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).
- Ma Q, Wang Y, Zhang W, Du Z, Tian Z, Li H. The Mechanism Involved in the Inhibition of Resveratrol and Genistein on the Contractility of Isolated Rat Uterus Smooth Muscle. Nutrients 2024 Oct 9;16(19).
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