Expression of proinflammatory cytokines IL-1β, IL-6 and TNFα in the retained placenta of mares.
Abstract: Retained fetal membranes (RFM) is a prevalent postpartum disease in mares. During parturition, various proinflammatory cytokines are released in the placenta, which further facilitates uterine contractions, expulsion of the fetus and fetal membranes. We hypothesized that an altered inflammatory response in mares results in retained fetal membranes. Samples of the endometrium and the allantochorion were collected from 15 mares with RFM and from 29 control mares within 2 h of foal delivery. Next, the mRNA expression of IL-1β, IL-6 and TNFα proteins was analyzed by Real Time PCR and Western blot. These cytokines were also localized by immunocytochemistry. In mares with RFM, the mRNA expression of IL-1β in the endometrium (p < 0.05) and IL-6 in the allantochorion (p < 0.0001) was higher than in mares that expelled fetal membranes physiologically. Higher expression of IL-6 in the allantochorion was confirmed by Western blot. In contrast, no changes in TNFα mRNA and protein expression were observed between the 2 groups of mares. Moreover, TNFα mRNA was barely detectable. The presence of all studied cytokine proteins in the allantochorion was confirmed by immunocytochemistry. The results suggest that the outbreak of inflammation is involved in the mechanism of placenta release in mares. Increased expression of IL-6 in the allantochorion and IL-1β in the endometrium could reflect a local immune response which leads to the detachment of fetal membranes. The low expression of TNFα mRNA might suggest that this cytokine is not involved in the expulsion of fetal membranes. Further work is needed to determine the exact role and timing of inflammatory activation in fetal membranes during equine parturition.
Copyright © 2018 Elsevier Inc. All rights reserved.
Publication Date: 2018-11-27 PubMed ID: 30503761DOI: 10.1016/j.theriogenology.2018.11.029Google Scholar: Lookup
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Summary
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The research article focuses on the connection between proinflammatory cytokines and postpartum disease in horses, particularly retained fetal membranes (RFM). It finds that higher levels of certain cytokines may be related to RFM and suggests further research to fully understand the role of these proteins during equine parturition.
Introduction to the Study and Hypothesis
- The researchers began by noting the problem of retained fetal membranes (RFM) as a common postpartum disease in mares. This condition occurs when the placenta, which houses and supports the fetus during pregnancy, does not fully expel after giving birth.
- The possible cause of RFM, according to the researchers, could be an irregular inflammatory response involving proinflammatory cytokines. These are proteins that aid in immune responses including the onset of inflammation. They are released during the birthing process to enhance uterine contractions and facilitate expulsion of the fetus and fetal membranes.
Methods of the Study
- The team collected samples from both the endometrium (inner lining of the uterus) and the allantochorion (fetal sac within the placenta) of 15 mares with RFM and 29 control mares, within 2 hours of foal delivery.
- The mRNA expression of the proinflammatory cytokines IL-1β, IL-6, and TNFα in these samples were analyzed using Real Time PCR and Western blot – laboratory techniques for determining gene and protein expression.
- An additional process used was immunocytochemistry, which visualizes and locates specific proteins in cells.
Results of the Research
- The results showed that in mares with RFM, the mRNA expression of IL-1β in the endometrium and IL-6 in the allantochorion was significantly higher than in mares who had successfully expelled the placenta. The increased IL-6 protein expression in the allantochorion was consistent with the mRNA expression results.
- However, there were no visible changes in the TNFα mRNA and protein expression in mares with RFM compared to mares without the condition, with TNFα mRNA barely detectable.
- All the cytokines under study were confirmed to be present in the allantochorion through immunocytochemistry.
Conclusions and Future Directions
- The study suggests that the onset of inflammation, governed by certain proinflammatory cytokines, plays a role in the detachment and expulsion of the placenta in mares.
- The increased expression of IL-1β in the endometrium and IL-6 in the allantochorion may denote a local immune response that contributes to the detachment of fetal membranes.
- The low expression of TNFα may point towards its possible irrelevance in the expulsion process of fetal membranes.
- However, more research is needed to understand the exact role and timing of these cytokines during equine parturition.
Cite This Article
APA
Jaworska J, Janowski T.
(2018).
Expression of proinflammatory cytokines IL-1β, IL-6 and TNFα in the retained placenta of mares.
Theriogenology, 126, 1-7.
https://doi.org/10.1016/j.theriogenology.2018.11.029 Publication
Researcher Affiliations
- Department of Animal Reproduction with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn; Oczapowskiego 14; 10-719, Olsztyn; Poland. Electronic address: joanna.jaworska@uwm.edu.pl.
- Department of Animal Reproduction with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn; Oczapowskiego 14; 10-719, Olsztyn; Poland.
MeSH Terms
- Animals
- Female
- Horse Diseases / metabolism
- Horses
- Immunohistochemistry
- Interleukin-1beta / metabolism
- Interleukin-6 / metabolism
- Placenta / metabolism
- Placenta, Retained / metabolism
- Placenta, Retained / veterinary
- Pregnancy
- RNA, Messenger / metabolism
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 9 times.- Oldenburg KS, Eaves LA, Smeester L, Santos HP, O'Shea TM, Fry RC. Development of the genomic inflammatory index (GII) to assess key maternal antecedents associated with placental inflammation. Placenta 2021 Aug;111:82-90.
- Jaworska J, Ropka-Molik K, Piórkowska K, Szmatoła T, Kowalczyk-Zięba I, Wocławek-Potocka I, Siemieniuch M. Transcriptome Profiling of the Retained Fetal Membranes-An Insight in the Possible Pathogenesis of the Disease. Animals (Basel) 2021 Mar 3;11(3).
- Dong M, Hou Y, Ding X. Structure identification, antitumor activity and mechanisms of a novel polysaccharide from Ramaria flaccida (Fr.) Quél. Oncol Lett 2020 Sep;20(3):2169-2182.
- Silva P, de Almeida M, Silva J, Albino S, Espírito-Santo R, Lima M, Villarreal C, Moura R, Santos V. (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential. Int J Mol Sci 2020 Apr 8;21(7).
- Jaworska J, Ropka-Molik K, Wocławek-Potocka I, Siemieniuch M. Inter- and intrabreed diversity of the major histocompatibility complex (MHC) in primitive and draft horse breeds. PLoS One 2020;15(2):e0228658.
- Zhang Z, Guo S, Yang J, Hou X, Zhang X, Liu H, Liu T, Jin Y. Early-Onset Negative Energy Balance in Transition Dairy Cows Increases the Incidence of Retained Fetal Membranes. Animals (Basel) 2026 Jan 13;16(2).
- Aránguiz F, Bahamonde J, Sales F, Araya M, Ulloa-Leal C, Ratto M, Sandoval C. Comparison Between Two Methodologies of Sample Preservation for RNA Extraction in Naturally Delivered Ovine Placenta. Animals (Basel) 2025 Mar 10;15(6).
- Dos Santos Silva P, Kra G, Butenko Y, Daddam JR, Levin Y, Zachut M. Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows. J Anim Sci Biotechnol 2024 May 21;15(1):74.
- Morales-Vázquez MM, Meza-Serrano E, Lara-Pereyra I, Acuña-González RJ, Alonso-Morales R, Hayen-Valles S, Boeta AM, Zarco L, Lozano-Cuenca J, López-Canales JS, Flores-Herrera H. Equine Placentitis in Mares Induces the Secretion of Pro-Inflammatory Cytokine eIL-1β and the Active Extracellular Matrix Metalloproteinase (MMP)-9. Vet Sci 2023 Aug 22;10(9).
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