Preimplantation factor modulates acute inflammatory responses of equine endometrium.
Abstract: Persistent mating-induced endometritis (PMIE) is a significant cause of mare infertility hence its treatment would advance the management of susceptible mares. Preimplantation factor (PIF) is secreted by viable embryos, including human, mouse and cattle, and is essential for maternal immune-tolerance without immune-suppression by modulating inflammation. This preliminary study aimed to test whether PIF exerts inflammatory-modulating properties upon equine endometrium challenged with Escherichia coli-derived lipopolysaccharide (LPS) using endometrial explant culture. Follicular (n = 3), luteal (n = 4), anoestrous (n = 4) and transitional (n = 4) stage endometrial explants were established and cultured in triplicate in either serum-free medium alone (control) or medium with; 50 or 100 nmol/L synthetic PIF (sPIF); 3 μg/mL LPS; LPS and 50 or 100 nmol/L sPIF; or scrambled PIF (PIFscr; same amino acid composition arranged in a different order). Media samples were collected at 24 and 72 h, representing acute and chronic inflammatory response. Radioimmunoassay determined Prostaglandin F (PGF ) as an inflammatory marker. The only significant observation was the abrogation of PGF response to LPS challenge by 100 nmol/L PIF for follicular stage tissue, 24 h after treatment. Further studies are therefore, warranted to realise PIF potential in managing PMIE.
© 2018 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.
Publication Date: 2018-10-01 PubMed ID: 30273998PubMed Central: PMC6236140DOI: 10.1002/vms3.126Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research explores the potential of using Preimplantation factor (PIF) in regulating inflammation within the equine endometrium (horse womb tissue), particularly in response to challenges from bacteria-derived substances, as a way of treating mare infertility caused by Persistent mating-induced endometritis (PMIE).
Background
- This study is based on the need to find better treatment options for Persistent mating-induced endometritis (PMIE), inflammation of the womb after mating, which is a chief cause of infertility in mares.
- Previously, Preimplantation factor (PIF), a compound secreted by viable embryos in various species including humans, mice and cows, was found to play an essential role in promoting maternal immune-tolerance. It does this by moderating inflammation, without suppressing the immune system.
Aim and Methodology
- The primary objective of the study was to test if synthetic PIF (sPIF) could modify inflammatory responses in the womb tissues of horses when confronted with Escherichia coli (E.coli)-derived lipopolysaccharide(LPS).
- For this, endometrial explants (small pieces of endometrial tissue in culture) were prepared from horse womb tissues at various reproductive stages – follicular, luteal, anoestrous, and transitional.
- These explants were exposed to either nothing (control), or sPIF (50 or 100 nmol/L), or LPS (3 µg/mL), or a combination of LPS and sPIF (50 or 100 nmol/L), or an altered form of PIF (scrambled PIF).
Results and conclusion
- The only significant observation made was that a concentration of 100 nmol/L sPIF was able to halt the release of Prostaglandin F (PGF, a marker of inflammation) in the follicular-stage tissue when challenged with LPS, 24 hours after treatment.
- This preliminary find calls for further research to fully understand the potential of PIF in managing the inflammatory problems associated with horse reproduction and consequently, infertility.
Cite This Article
APA
Nash DM, Paddison J, Davies Morel MCG, Barnea ER.
(2018).
Preimplantation factor modulates acute inflammatory responses of equine endometrium.
Vet Med Sci, 4(4), 351-356.
https://doi.org/10.1002/vms3.126 Publication
Researcher Affiliations
- Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Penglais, Aberystwyth, UK.
- Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Penglais, Aberystwyth, UK.
- Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Penglais, Aberystwyth, UK.
- Society for the Investigation of Early Pregnancy, Cherry Hill, New Jersey, USA.
MeSH Terms
- Animals
- Dinoprost / metabolism
- Endometrium / drug effects
- Female
- Horses
- Inflammation / drug therapy
- Inflammation / metabolism
- Inflammation / veterinary
- Pregnancy Proteins / metabolism
- Tissue Culture Techniques
Grant Funding
- Biotechnology and Biological Sciences Research Council
References
This article includes 22 references
- Allen WE, Pycock JF. Current views on the pathogenesis of bacterial endometritis in mares.. Vet Rec 1989 Sep 9;125(11):298-301.
- Barnea ER. Insight into early pregnancy events: the emerging role of the embryo.. Am J Reprod Immunol 2004 May;51(5):319-22.
- Barnea ER, Kirk D, Ramu S, Rivnay B, Roussev R, Paidas MJ. PreImplantation Factor (PIF) orchestrates systemic antiinflammatory response by immune cells: effect on peripheral blood mononuclear cells.. Am J Obstet Gynecol 2012 Oct;207(4):313.e1-11.
- Bucca S, Carli A, Buckley T, Dolci G, Fogarty U. The use of dexamethasone administered to mares at breeding time in the modulation of persistent mating induced endometritis.. Theriogenology 2008 Oct 15;70(7):1093-100.
- Christoffersen M, Troedsson M. Inflammation and fertility in the mare.. Reprod Domest Anim 2017 Aug;52 Suppl 3:14-20.
- Duzyj CM, Barnea ER, Li M, Huang SJ, Krikun G, Paidas MJ. Preimplantation factor promotes first trimester trophoblast invasion.. Am J Obstet Gynecol 2010 Oct;203(4):402.e1-4.
- Fumuso EA, Aguilar J, Giguère S, Rivulgo M, Wade J, Rogan D. Immune parameters in mares resistant and susceptible to persistent post-breeding endometritis: effects of immunomodulation.. Vet Immunol Immunopathol 2007 Jul 15;118(1-2):30-9.
- Gores-Lindholm AR, LeBlanc MM, Causey R, Hitchborn A, Fayrer-Hosken RA, Kruger M, Vandenplas ML, Flores P, Ahlschwede S. Relationships between intrauterine infusion of N-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy, and reproductive performance.. Theriogenology 2013 Aug;80(3):218-27.
- Herath S, Fischer DP, Werling D, Williams EJ, Lilly ST, Dobson H, Bryant CE, Sheldon IM. Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus.. Endocrinology 2006 Jan;147(1):562-70.
- Hughes JP, Loy RG. The relation of infection to infertility in the mare and stallion.. Equine Vet J 1975 Jul;7(3):155-9.
- Katila T. Sperm-uterine interactions: a review.. Anim Reprod Sci 2001 Dec 3;68(3-4):267-72.
- LeBlanc MM. Advances in the diagnosis and treatment of chronic infectious and post-mating-induced endometritis in the mare.. Reprod Domest Anim 2010 Jun;45 Suppl 2:21-7.
- Melkus E, Witte T, Walter I, Heuwieser W, Aurich C. Investigations on the endometrial response to intrauterine administration of N-acetylcysteine in oestrous mares.. Reprod Domest Anim 2013 Aug;48(4):591-7.
- Nash D, Lane E, Herath S, Sheldon IM. Endometrial explant culture for characterizing equine endometritis.. Am J Reprod Immunol 2008 Feb;59(2):105-17.
- Nash DM, Sheldon IM, Herath S, Lane EA. Markers of the uterine innate immune response of the mare.. Anim Reprod Sci 2010 May;119(1-2):31-9.
- Paidas MJ, Krikun G, Huang SJ, Jones R, Romano M, Annunziato J, Barnea ER. A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells.. Am J Obstet Gynecol 2010 May;202(5):459.e1-8.
- Pycock JF, Newcombe J. The relationship between intraluminal fluid, endometritis, and pregnancy rate in the mare. Equine Practice 18, 19–22.
- Roussev RG, Dons'koi BV, Stamatkin C, Ramu S, Chernyshov VP, Coulam CB, Barnea ER. Preimplantation factor inhibits circulating natural killer cell cytotoxicity and reduces CD69 expression: implications for recurrent pregnancy loss therapy.. Reprod Biomed Online 2013 Jan;26(1):79-87.
- Stamatkin CW, Roussev RG, Stout M, Absalon-Medina V, Ramu S, Goodman C, Coulam CB, Gilbert RO, Godke RA, Barnea ER. PreImplantation Factor (PIF) correlates with early mammalian embryo development-bovine and murine models.. Reprod Biol Endocrinol 2011 May 15;9:63.
- Watson ED, Stokes CR, David JS, Bourne FJ. Effect of ovarian hormones on promotion of bactericidal activity by uterine secretions of ovariectomized mares.. J Reprod Fertil 1987 Mar;79(2):531-7.
- Wingfield Digby NJ, Ricketts SW. Results of concurrent bacteriological and cytological examinations of the endometrium of mares in routine stud farm practice 1978-1981.. J Reprod Fertil Suppl 1982;32:181-5.
- Woodward EM, Christoffersen M, Horohov D, Squires EL, Troedsson MH. The effect of treatment with immune modulators on endometrial cytokine expression in mares susceptible to persistent breeding-induced endometritis.. Equine Vet J 2015 Mar;47(2):235-9.
Citations
This article has been cited 4 times.- Monteiro de Barros MR, Davies-Morel MCG, Mur LAJ, Creevey CJ, Alison RH, Nash DM. Characterization of an Ex Vivo Equine Endometrial Tissue Culture Model Using Next-Generation RNA-Sequencing Technology. Animals (Basel) 2021 Jul 3;11(7).
- Santos ED, Moindjie H, Sérazin V, Arnould L, Rodriguez Y, Fathallah K, Barnea ER, Vialard F, Dieudonné MN. Preimplantation factor modulates trophoblastic invasion throughout the decidualization of human endometrial stromal cells. Reprod Biol Endocrinol 2021 Jun 27;19(1):96.
- Wonfor RE, Creevey CJ, Natoli M, Hegarty M, Nash DM, Rose MT. Interaction of preimplantation factor with the global bovine endometrial transcriptome. PLoS One 2020;15(12):e0242874.
- Merhi Z, Garg B, Moseley-LaRue R, Moseley AR, Smith AH, Zhang J. Ozone therapy: a potential therapeutic adjunct for improving female reproductive health. Med Gas Res 2019 Apr-Jun;9(2):101-105.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists