Oxytocin stimulated release of PGF2α and its inhibition by a cyclooxygenase inhibitor and an oxytocin receptor antagonist from equine endometrial cultures.
Abstract: Uterine inflammation results in a poor uterine environment and early embryonic loss in the mare due to an inhibition of maternal recognition of pregnancy caused from increased prostaglandin F2α (PGF2α). Oxytocin binds to endometrial cell receptors to activate prostaglandin synthesis. An oxytocin receptor antagonist (Atosiban) and a cyclooxygenase inhibitor (indomethacin) both decrease PGF2α production. The aim of this study was to evaluate the in vitro effects of Atosiban and indomethacin on equine uterine prostaglandin secretion. Equine endometrial explants were harvested on day two of behavioral estrus. Endometrial explant cultures were challenged with oxytocin (250nM) and PGF2α concentrations were measured over time. Explants were also cultured with Atosiban and indomethacin for 6h to determine the influence on PGF2α secretion. When endometrial explants were challenged with oxytocin, PGF2α concentrations were greater (P<0.0001) at each time point over the 24h of culture as compared to controls. Oxytocin failed (P<0.001) to elicit PGF2α release in explants cultured with either Atosiban or indomethacin. These findings show equine endometrial explants can be stimulated with oxytocin to increase secretion of PGF2α and this secretion can be inhibited through an oxytocin receptor antagonist and a Cox inhibitor, suggesting that this response to oxytocin involves an oxytocin receptor mediated event that activates the prostaglandin synthesis cascade through cyclooxygenase. Furthermore, this data suggests a role for the use of these inhibitors in vivo to decrease uterine PGF2α secretion and prevent early luteal regression and embryonic loss.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication Date: 2013-04-24 PubMed ID: 23664650DOI: 10.1016/j.anireprosci.2013.04.010Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research article investigates how oxytocin affects horse uterine tissue and the potential use of inhibitors to reduce the production of a compound that leads to uterine inflammation and early embryonic loss.
Objective of the Research
- The research aimed to understand the role of oxytocin in stimulating the production of prostaglandin F2α (PGF2α) in horse uterine tissue, and the effects of inhibitors, Atosiban (oxytocin receptor antagonist) and indomethacin (a cyclooxygenase inhibitor), in reducing this production.
Methodology
- The researchers used equine endometrial explants (samples of horse uterine tissue) taken on the second day of behavioral estrus (part of the mare’s reproductive cycle).
- These tissue samples were then exposed to oxytocin to stimulate the production of PGF2α and their concentrations over time were measured.
- Further experiments were carried out on these samples, in which they were cultured with Atosiban and indomethacin for 6 hours, to see how these inhibitors affected PGF2α secretion.
Findings
- In the presence of oxytocin, PGF2α concentrations were significantly higher in each time point over a 24-hour culture period compared to controls.
- Oxytocin did not elicit PGF2α release in samples cultured with either Atosiban or indomethacin, revealing that these inhibitors were effective in curbing the production of PGF2α.
Implications of the Study
- These findings suggest that the secretion of PGF2α in response to oxytocin is an event mediated by an oxytocin receptor that activates the prostaglandin synthesis cascade through cyclooxygenase.
- The study provides a foundation for potential in vivo applications of these inhibitors to reduce horse uterine PGF2α secretion. Lowering this secretion may prevent early embryonic loss, an issue that could have significant implications for the equine breeding industry.
Cite This Article
APA
Penrod LV, Allen RE, Rhoads ML, Limesand SW, Arns MJ.
(2013).
Oxytocin stimulated release of PGF2α and its inhibition by a cyclooxygenase inhibitor and an oxytocin receptor antagonist from equine endometrial cultures.
Anim Reprod Sci, 139(1-4), 69-75.
https://doi.org/10.1016/j.anireprosci.2013.04.010 Publication
Researcher Affiliations
- Department of Animal Sciences, William J. Parker Agricultural Research Center, The University of Arizona, Tucson, AZ 85719, USA. penrodl@email.arizona.edu
MeSH Terms
- Animals
- Biopsy / veterinary
- Cyclooxygenase Inhibitors
- Dinoprost / metabolism
- Endometrium / drug effects
- Endometrium / metabolism
- Female
- Hormone Antagonists / pharmacology
- Horses / metabolism
- Indomethacin / pharmacokinetics
- Least-Squares Analysis
- Organ Culture Techniques
- Oxytocin / pharmacology
- Receptors, Oxytocin / antagonists & inhibitors
- Vasotocin / analogs & derivatives
- Vasotocin / pharmacology
Citations
This article has been cited 3 times.- Wang R, Huang H, Tan Y, Xia G. Efficacy of atosiban for repeated embryo implantation failure: A systematic review and meta-analysis.. Front Endocrinol (Lausanne) 2023;14:1161707.
- Mondal A, Maity TK, Bishayee A. Analgesic and Anti-Inflammatory Activities of Quercetin-3-methoxy-4'-glucosyl-7-glucoside Isolated from Indian Medicinal Plant Melothria heterophylla.. Medicines (Basel) 2019 May 27;6(2).
- Chilumuri A, Milton NG. The Role of Neurotransmitters in Protection against Amyloid- β Toxicity by KiSS-1 Overexpression in SH-SY5Y Neurons.. ISRN Neurosci 2013;2013:253210.
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